Chemistry Reference
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been estimated.
1a
As a consequence, spontaneous DNA degradation occurs mainly
through different pathways, involving either C-O cleavage, nucleobase ring opening
or radical attack (Figure 13.2).
1a
Metal ions can assist the P-O hydrolytic cleavage of phosphodiesters in differ-
ent ways (Figure 13.3). Acting as Lewis acids, they can activate the phosphate group
toward the attack of the nucleophile, increase the leaving group ability of the depart-
ing alcohol and activate a metal-coordinated water molecule as a nucleophile.
1b
Moreover, indirect activation modes are possible, with metal bound hydroxides or
water molecules performing general base or acid catalysis. As observed in many
enzymatic processes, several metal centers may act cooperatively to accelerate these
mechanistic steps. Accordingly, multinuclear complexes are often more active than
their mononuclear counterparts.
1b
The exceptional high resistance of DNA toward hydrolysis makes even a simple
kinetic investigation of the cleavage process quite challenging. However, super-
coiled plasmid DNA is a more accessible substrate and, because of this, very popular
Figure 13.2
Alternative DNA degradation pathways
Figure 13.3
Possible activation modes provided by metal ions for acceleration of the hydrol-
ysis of phosphate diesters
