Chemistry Reference
In-Depth Information
trivalent lanthanide ions. At pH 7.0 and 50 °C, the half-life of the dinucleotide TpT
is reduced to 3.6 hours, which amounts to more than 11 orders of magnitude rate
acceleration over the spontaneous hydrolysis reaction.
10a,12
As a result, Ce(IV) is 20
to 1000 times more effi cient than any other trivalent lanthanide, with comparable
high effi cacy toward single- and double-stranded linear DNA.
13
The source of this
remarkable reactivity has been attributed by Komiyama and coworkers to the great
electron-withdrawing ability of this tetravalent ion.
3m
Surprisingly, free Ce(IV) ions
are inactive in promoting plasmid DNA hydrolysis, probably due to steric hindrance
between the Ce(IV) hydroxide gels, which form at neutral pH, and the substrate.
14
In fact, when converted into homogeneous solutions by the addition of solubilizing
agents (dextran, polyvinylpirrolidone), Ce(IV) recovers activity toward plasmid
DNA and is about ten times more reactive than trivalent lanthanide ions.
15
Aqueous lanthanide ions are toxic for biological systems and, more generally,
free metal ions are not suitable candidates for preparing appealing catalysts. The
formation of stable complexes with proper ligands is therefore mandatory. However,
this task turns out to be quite diffi cult in the case of lanthanide ions for two reasons:
(i) they undergo very facile ligand exchange; (ii) the catalytic activity requires an
unsaturated coordination sphere to allow interaction with water (nucleophile) and
the substrate. Stable complexes can be obtained by using polyaminocarboxylate
derivatives, crown ethers or azacrown ligands.
3i
In many cases, however, the forma-
tion of the complex results in a lower reactivity than that observed with the free
metal ions, particularly in the case of polyaminocarboxylate complexes, due to the
decrease in the overall charge of the complex and to the saturation of the metal ion
coordination sphere. Neutral ligands, such as azacrowns or crown ethers, are thus
more suitable, in order to retain the reactivity of the free metal ion, although their
coordination strength is not so high and the complexing agent must be used in large
excess to ensure complete formation of soluble complexes.
16
In the case of Ce(IV), the reactivity decrease brought about by the use of
anionic ligands leads to an interesting substrate selectivity. In fact, the Ce(IV)-
EDTA complex is able to cleave single-stranded DNA (ssDNA), but not double-
stranded DNA (dsDNA).
17
The reaction is slow, but highly selective and, as a
consequence, gap sites or bulges present in a dsDNA that expose short sequences
of ssDNA are cleaved without touching the rest of the macromolecule.
18
Such
behaviour is the basis of the ARCUT system proposed by Komiyama and cowork-
ers,
5
which will be described in detail later.
Metal ions other than lanthanides are scarcely active in promoting DNA
hydrolysis. Nevertheless, a few mononuclear metal complexes have been reported
to act as artifi cial nucleases. The Co(III)-TAMEN complex (Figure 13.6) cleaves
plasmid DNA, at 37 °C and pH 7.6, with a fi rst - order rate constant of 5
10
− 5
s
− 1
.
19
Although the concentration of complex required, 1mM, is relatively high, suggesting
a poor interaction with the substrate, the mechanism is fully hydrolytic, as the nicked
DNA can be religated. This complex is also active toward single-stranded DNA.
Zn(II) is one of the metal ions most frequently found in hydrolytic metallo-
enzymes, but the activities reported for simple mononuclear complexes are
usually low. One remarkable exception is the Zn(II)-BHTDE complex (BHDTE =
N,N
×
′
-bis(benzylhistidyl)diethylenetriamine, Figure 13.7) reported by Ichikawa and
