Chemistry Reference
In-Depth Information
ligand-modified PNA duplexes may also be due to the fact that not only the geometry
but also the stability constants of complexes of Cu
2þ
with
5Q
and of Ni
2þ
with
Bpy
ligands are also different.
Ni
2þ
binding to the ligand-modified duplexes increased the melting temperature of
the
Pyr
P
-
and
Pur
P
-
modified DNA duplexes by the same number of degrees. This is
surprising to some degree given the fact that there are geometric differences between
the
Pyr
P
Ni
2
þ
Pur
P
complexes; the size of the former complex
(estimated as distance between corresponding atoms bound to the backbone, i.e.,
Ni
2
þ
Pyr
P
and
Pur
P
9A
; Figure 10.1).
The stabilization conferred to the DNA or PNA duplexes by the [ML
2
] complexes
with
Bpy
,
Pur
P
,or
Pyr
P
ligands is at most equal to that of a GC base pair, despite the
fact that the complexes contain coordination bonds, which are stronger than hydrogen
bonds. This discrepancy may be due to the fact that in [ML
2
] complexes, the two aro-
matic cis-diimine ligands cannot be strictly coplanar, because of the steric clash
between the 3,3
0
-protons of the carbon atoms adjacent to the nitrogens. As a conse-
quence, these complexes undergo either a tetrahedral or a bow-step distortion [52]. In
general, p-stacking interactions between the [M(
Bpy
)
2
] complexes in solid state favor
the latter distortion. DFT calculations for the [Ni(
Pur
P
)
2
]
2þ
also predict a “bow-step”
square planar geometry, which may be further reinforced by stacking interactions
between the
Pur
P
ligands and adjacent nucleobases [13b].
The change in melting temperature induced by DNA binding of a 3d divalent, transi-
tion metal ion to the
Pyr
P
or
Pur
P
ligands in modified duplexes decreased in the order
Ni
2þ
>
5A
) is significantly smaller than that of a natural base pair (
Mn
2þ
(Table 10.1, entry 4-5). This trend is
similar to that observed for the 10-bp PNA duplexes that contained a pair of bipyridine
ligands [16c] and it correlates with that of the increasing stability constants for metal
complexes of bipyridine. Cu
2þ
represents an exception, which could be due to the rela-
tionship between steric constraints exerted by the duplex and Jahn Teller distortion at
the Cu
2þ
.
A bis(pyridopurine) ligand site has been also introduced in GNA duplexes [53]. Ni
2þ
binding to the ligand-modified GNA duplex caused a large increase in the
T
m
of the
duplex (larger than that caused by Cu
2þ
and several other transition metal ions). In
contrast, a GNA duplex with the same sequence but containing a pair of hydroxypyr-
idone ligands was stabilized to the largest extent by Cu
2þ
(see below p. 357).
Co
2þ
>
Cu
2þ
>
Fe
2þ
Zn
2þ
O,N-Coordinating Ligands: 2-Aminophenol, 8-Hydroxyquinoline, and Salen. Ortho-
aminophenol [9b-d] (
AP
) in its benzyl-protected form was incorporated in a ligandoside,
which in turn was used to synthesize two complementary DNA strands with a central pair
of
AP
ligands (Table 10.1, entry 6 and Figure 10.7). The thermal stability of the 21-bp
DNA duplex formed from these two strands was slightly lower than that of a duplex with
an AT base pair instead of the pair of
AP
ligands, both in the absence and presence of
Cu
2þ
.ThefactthatCu
2þ
binding did not affect the stability of the AP-modified DNA
duplex can be attributed to the fact that the benzyl protection group renders the ligand
significantly bulkier than the A or T bases and reduces the binding affinity of the ligand
for metal ions [54].
8-Hydroxyquinoline (
Q
) has been used for the efficient incorporation of metal ions into
DNA, PNA and GNA duplexes. In this section, we understand by GNA duplex, a DNA
Search WWH ::
Custom Search