656
Bioinorganic Chemistry
Though these lifetimes refer to water
exchange in the wholly aquated metal
ions, they also reflect the relative rates
of exchange of other ligands. When bound
to a metal ion, other ligands, including
hydroxide
ion,
increase
modestly
the
release rate of bound water, typically by
about 10
2
. As a poorer leaving group,
hydroxide
ion
itself
exchanges
much
more slowly than water. Chelated ligands
exchange more slowly, but again, the
relative order prevails. In the case of
chelates, binding occurs Frst by one
donor group followed by chelate ring
closure. In some cases, such as Fve-
membered rings, the chelate ring closes
rapidly, and in others, especially with
larger rings, ring closure may become the
slow step. Selective broadening of lines in
nuclear magnetic resonance spectroscopy
that have
been used to
indicate the
binding site of a paramagnetic metal ion at
stoichiometric concentrations often fails.
This occurs because chelate ring closure
is slow compared to rapid passage of
the metal ion to other ligands present
in large excess, which bind only in a
unidentate mode.
We conclude with an application that
incorporates many of the principles men-
tioned in this chapter. Surprisingly, the
above exchange rate series demonstrates
that some of the strongest-binding metal
ions undergo the most rapid ligand ex-
change. Examples from the high-rate end
of the series include Pb
2
+
,Hg
2
+
,Cu
2
+
,
and Cd
2
+
, all strong ligand binders. A sig-
niFcant feature of the toxicology of Hg
2
+
and CH
3
Hg
+
is the rapid exchange of lig-
ands in and out of coordination to the
metal ion. ±or CH
3
Hg
+
binding to the
sulfhydryl group of glutathione (present
in blood plasma at 4 mM), the stability-
constant logarithm is an extraordinary
log
K
=
15
.
9. ±or such strong binding,
the half-life for exchange by a dissocia-
tive mechanism is about 10 days. Yet, the
average lifetime for the CH
3
HgSR com-
plex in the presence of excess glutathione
is less than 0.01 s. This comparison shows
that exchange does not occur by a disso-
ciative mechanism. The ability of linear
two-coordinated Hg
2
+
and CH
3
Hg
+
to as-
sociate weakly with additional donor atoms
accounts for rapid metal ion exchange
among donor atoms. The last two ligands
are bound much more weakly than the Frst
two and exhibit longer Hg-to–donor atom
bond lengths. Excess ligand participates
in nucleophilic attack at an uncoordinated
site on the metal ion with rearrangement
in the coordination geometry and release
of a formerly bound ligand. This addi-
tion–elimination mechanism accounts for
the very rapid exchange in Hg
2
+
and
CH
3
Hg
+
complexes.
See also
Bioorganic Chemistry; Cal-
cium Biochemistry.
Bibliography
Books and Reviews
Berthon, G. (Ed.) (1995)
Handbook of Metal-
Ligand
Interactions
in
Biological
Fluids:
Bioinorganic Chemistry, Vols. 1 and 2 and
Bioinorganic Medicine, Vols. 1 and 2
,M
a
r
c
e
l
Dekker, New York.
Bertini, I., Sigel, A., Sigel, H. (2001)
Handbook
on Metalloproteins
, Marcel Dekker, New York.
da Silva, J.J.R.±., Williams, R.J.P. (2001)
The
Biological
Chemistry
of
the
Elements
,2
n
d
edition, Clarendon Press, Oxford.
Holm, R.H.,
Solomon, E.I.
(Eds.)
(1996)
Bioinorganic Enzymology,
Chem.
Rev.
96
,
2237–3042. Thematic issue with 24 articles.
Kaim, W., Schwederski, B. (2000)
Bioinorganic
Chemistry: Inorganic Elements in the Chemistry
of Life
,Wiley,Chichester.
previous page 656 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 658 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off