644
Bioinorganic Chemistry
8
Hard and Soft Acids and Bases
8.1
DeFnitions
More than 45 years ago, metal ions were
divided into two groups: a majority la-
beled class (a) for which the anion-binding
strength in aqueous solutions is greatest
for F
and generally follows the order
F
>
Cl
>
Br
>
I, and a minority class
(b) in which F
binding is weaker than
at least one of the heavier anions and gen-
erally follows the order F
<
Cl
<
Br
<
I
(in the gas phase, all metal ions follow the
±rst order). The same trends occur in other
columns in the periodic table; for example,
class (a) metal ions tend to favor binding
to oxygen and class (b) metal ions to sulfur
ligands. Subsequently, Pearson extended
the application and changed the terminol-
ogy so that class (b) metal ions became
soft and class (a) metal ions were subdi-
vided into hard and borderline groups. The
greater popularity of the altered nomen-
clature is partly because it is easier to say
harder or softer than more (a) character or
more (b) character. Thus, it is now said that
fluorideandch
loridearehard
,bromideis
borderline, and iodide is soft.
The dictum by Pearson that hard acids
prefer to interact with hard bases and soft
acids with soft bases has become well
known. In biochemistry, there are only
four main types of ligand donor atoms, of
which O and aliphatic N are classi±ed as
hard, aromatic N as borderline, and S as
soft bases. All alkali, alkaline earth, and
lanthanide ions are classi±ed as hard, as
are the ±rst ±ve metal ions in Table 3 and
Mn
2
+
. Borderline metal ions include the
last four of the stability ruler (Table 4) and
Zn
2
+
and Pb
2
+
. Soft metal ions include
Ag
+
,Cd
2
+
,CH
3
Hg
+
,andHg
2
+
.
Despite the popularity of the hard–soft
designation, there was a lapse of a quarter
century before Pearson proposed a quan-
titative scale. Pearson de±ned softness as
the reciprocal of hardness and presented
quantitative absolute hardness values for
metal ions and ligands (in which the hard-
ness of an atom and an anion such as F
and F
are identical). A few years later,
Pearson disavowed his quantitative hard-
ness scales for at least some cations and
anions. In any case, the hardness values
for metal ions do not correlate at all with
the stability constants of complexes, which
are correlated best by the electron af±nity
of the metal ion. Though often spoken of
by chemists as if it is the determining fac-
tor in complex stability, the contribution of
hardness or softness may pale when com-
pared to the intrinsic stability, which often
dominates the binding strength.
8.2
Substitution Reactions
Comparisons of hardness and softness,
like the stability order of halide complexes
mentioned in the ±rst paragraph, are
equivalent to describing the extent of
substitution (not exchange) reactions. We
quantitatively evaluate the free energy
change in the form of log stability-constant
differences of substitution reactions. If M
and N are two different metal ions and
X and Y two different ligands, we may
compare the hardness of a metal ion by
considering the substitution on the metal
ion of one ligand by another
MX
+
Y
−−−→
←−−−
X
+
MY
f
o
rw
h
i
c
ht
h
ef
r
e
ee
n
e
r
g
yc
h
a
n
g
ei
s
proportional to log
K
MY
–log
K
MX
,wh
e
r
e
K
MY
and
K
MX
are the stability constants
for complexes MY and MX respectively.
previous page 644 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 646 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off