Bioinorganic Chemistry
653
Comparison of the two series reveals a
marked promotion of the G7 and A7
sites on passing from the Frst to the
second series. Moreover, in the DNA dou-
ble helix, the N7 sites are not involved in
interstrand hydrogen bonding and are con-
sequently relatively exposed. Thus, the an-
titumor
cis
-diaminodichloroplatinum(II)
binds mainly at the guanosine N7 site of
DNA. The sugar moiety binds metal ions
very weakly and insigniFcantly.
Though proposed many times as metal
ion binding sites, primary amino (–NH
2
)
groups located at C4 in cytidine, C6 in
adenosine, and C2 in guanosine are nei-
ther proton nor metal ion binding sites in
neutral solutions. These amino groups are
not basic, the flat
NH
2
group is nearly
coplanar with the ring, and the amino ni-
trogen–to-carbon bond lengths are about
6-pm shorter in the nucleic bases than
in aniline. This combination of properties
indicates appreciable double-bond charac-
ter and extensive delocalization of electron
density into the rings. Consistent with
their appreciable
positive
charge density,
the primary amino groups serve as hydro-
gen bond donors in speciFc base pairing.
Moreover, in strongly acidifying solvents,
even the dication of cytosine and the tri-
cations of adenine and guanine have still
not undergone amino group protonation
as the ring nitrogens and O2 in cytosine
and O6 in guanine protonate before the
amino group. Only upon its deprotonation
in strongly basic solutions does the pri-
mary amino group (p
K
a
16) coordinate
a few strongly binding metal ions such as
CH
3
Hg
+
.
13.5
Nucleic Acids
With
the
introduction
of
more
than
one basic phosphate group, the di- and
tri-nucleotides (p
K
a
=
6
.
5) become strong
metal ion binders. Virtually all reactions
of ATP require a Mg
2
+
cofactor, and
ATP
occurs
as
a
Mg
2
+
complex
in
cells. Nucleic acid chemists were slow
to recognize the role of ambient metal
ions in stabilizing polymeric nucleic acid
structures. With a negative charge on
the
phosphate
of
each
residue,
only
a random-coil form exists at low salt
concentrations. The phosphate groups in
the polymers are not basic (p
K
a
1) and
bind metal ions very weakly. Required for
structures such as the double helix are
nonspeciFcally bound alkali metal ions
and Mg
2
+
serving as counterions to offset
thenega
t
ivecha
rge
sonthepho
spha
te
s
.
Mg
2
+
is also important in stabilizing
various RNA structures.
14
Dioxygen
It is impossible to overstate the effects
that increases in the dioxygen content of
thea
tmospherehavew
rough
tfo
rl
i
feon
Earth. On primitive Earth, the atmosphere
was free of dioxygen, and beginning about
3 500 million years ago, anaerobic prokary-
otes thrived. About 2 700 million years
ago, prokaryotes began emitting dioxy-
gen, and the atmospheric content began
increasing. Soluble ±e
2
+
was oxidized
to ±e
3
+
, which formed a very insoluble
goethite, ±e(OH)
3
, that allows only 10
20
Mfree±e
3
+
at pH 7.0. (±or a typical cell
volume of 10
12
L, this implies only one
±e
3
+
ionin10
8
cells!) Thus, this impor-
tant and formerly freely available element
became scarce, and it was necessary for
nature to Fnd new ways to handle it. The
ever-increasing dioxygen concentration be-
came an environmental catastrophe for an
anaerobe unable to Fnd a niche or evolve.
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