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duplex in the presence of Ni
2þ
(Table 10.2, entry 8) suggested that Ni
2þ
coordinates to the
Pur
P
ligands and that the staking of the base pairs was not affected by the metal com-
plexes. UV titrations of the
Bpy
-modified PNA duplexes showed that they coordinate
only two transition metal ions. Also the thermal stability of the PNA duplexes in the pres-
ence of three equivalents of Ni
2þ
was not higher than in the presence of two equivalents
(Table 10.2, entry 7) [16c]. The difference in behavior of the DNA and PNA duplexes,
each containing three adjacent pairs of bidentate ligands may be due to: (a) the fact that
the larger
Pur
P
ligand can form bis-ligand but not tris-ligand complexes, (b) the differ-
ence in duplex length (i.e., 15-bp DNA duplex vs 10-bp PNA duplex), and/or (c) the
DNA backbone can act as a counteranion for the positively-charged complex, thus reduc-
ing the electrostatic repulsion between the adjacent [M
L
n
]
2þ
complexes, while the PNA
backbone is neutral.
Given the complexity of the coordination possibilities to duplexes containing multiple
ligands, structural information obtained by X-ray crystallography or NMR spectroscopy
can provide valuable information on the relative position of the ligands and metal com-
plexes with respect to the duplexes. Several structural studies of DNA, PNA, and GNA
duplexes containing ligands and/or metal complexes have been published in the last dec-
ade. Brotschi proposed a structural model for the DNA duplexes with consecutive
Bpy
Bpy
pairs in which the
Bpy
ligands form a zipper-like, interstrand stacking motif.
The bipyridines have their distal rings involved in p-stacking interactions and the DNA
backbone is stretched [70b]. The zipper model was confirmed by NMR studies of a 10-bp
DNA duplex that contained one central pair of biphenyl groups [71]. In contrast to this
model for structural organization of
Bpy
in DNA, the crystal structure of a 9-bp PNA
duplex with a central
Bpy
Bpy
pair showed that the two
Bpy
s are bulged out of the PNA
duplex and participate in intermolecular p-stacking interactions with each other. The
PNA duplex “collapsed” to allow the non-modified base pairs adjacent to the
Bpy
Bpy
pair to participate in regular p-stacking interactions with each other. Interestingly, the
effect of bulging out of the PNA duplex of the two
Bpy
s causes a
53
bending of the
duplex, which is significantly larger than the corresponding angle of the non-modified 8-
bp PNA (
25
) and is similar to that observed for a DNA duplex containing a synthetic
cis-syn-cyclobutane-pyrimidine dimer-like lesion in its complex with DNA photolyase
after
in situ
repair [72].
The crystal structure of a DNA duplex with a palindromic sequence d(5
0
-C
1
G
2
C
3
G
4
Di-
pic
5
A
6
T
7
Py
8
C
9
G
10
C
11
G
12
-3
0
) and containing two isolated
Dipic
-Cu
2þ
-
Py
complexes was
reported in 2001 [66]. In the duplex, the Cu
2þ
ions were coordinated by the
Dipic
and
Py
ligands in a square planar arrangement, with two additional donor atoms from adjacent
base pairs, namely the O4
0
of the T
7
nucleotide and the O6 of G
4
, weakly coordinated in
axial positions. The metal-containing DNA duplex had an alternating purine-pyrimidine
(APP) sequence, which is typical for Z-DNA. Indeed, the duplex adopted a Z conforma-
tion in both the crystal and the solution. The d(5
0
-C
1
G
2
C
3
G
4
A
5
Dipic
6
Py
7
T
8
C
9
G
10
C
11
G
12
-
3
0
) duplex that contained two
Dipic
Py
binding sites but did not have an APP sequence
adopted a B-conformation in solution and in the presence of Cu
2þ
ions. These structural
results suggest that the metal complex “conforms” to the DNA structure dictated by the
DNA sequence.
The structure of a palindromic DNA duplex containing three adjacent, central [
Tria-
zole
.Ag.
Triazole
] alternative base pairs was reported in 2010 [45]. Each of the three
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