Metal Complexes as Alternative Base Pairs or Triplets in Natural and Synthetic Nucleic Acid Structures - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 355

for other ligand-modified duplexes, replacement of an AT base pair with a pair of H lig-
ands in the middle of 15-bp DNA or GNA duplexes decreased the stability of the
duplexes. Binding of Cu 2þ to the H ligands led to a stabilization of the duplexes with
respect to both the non-modified and ligand-modified duplexes (Table 10.1, entry 8).
Zn 2þ and Co 2þ determined also an increase in the T m of the H -containing GNA duplexes,
while Ni 2þ ,Pd 2þ ,Ag þ , and Au 3þ did not affect the thermal stability of the duplexes.
The structure of two GNA duplexes that did not contain alternative base pairs [36,37]
and one GNA duplex containing two isolated [Cu H 2 ] alternative base pairs [59] have been
determined by X-ray crystallography. The high flexibility of the simplified backbone of
GNA underscores the relatively large structural differences observed between these
duplexes. The GNA duplexes have a helical pitch of 26 A with 10 bp per turn while the
metal-containing GNA duplex has a helical pitch of 60 A with 16 bp per turn. The [Cu H 2 ]
complex has a square planar geometry with a very small propeller twist between the
planes of the two H ligands. The complex has a C 0 1

C 0 1 backbone-backbone distance
larger by 2 A than a Watson-Crick base pair. This difference may be the reason why the
H ligandotides have an anti conformation while the nucleotides in Watson-Crick base
pairs have a gauche conformation with respect to the O3 0 -C3 0 -C2 0 -O2 0 torsion angle. In
contrast, in the backbone of each of two GNA duplexes that did not contain metal-based
alternative base pairs, the vicinal O3 0 -C3 0 and C2 0 -O2 0 bonds had a strictly alternating
gauche and anti conformation with each base pair containing one nucleotide in the gauche
and one in the anti conformation.
A potential application of metal-containing nucleic acid structures is in molecular
electronics. As a step towards building molecular devices based on duplexes that
contain metal-based alternative base pairs, Liu et al. assessed charge transport in
DNA duplexes containing one pair of H ligands in the presence of Cu 2þ [60], and
Wierzbinski et al. studied the charge transfer of Bpy -modified PNA duplexes in the
absence and presence of Zn 2þ [51]. Liu et al. conducted single molecule break junc-
tion experiments using single-wall carbon nanotubes as the electric contact for the
DNA duplexes. Wierzbinski et al. measured the electrochemical rate constants for
charge transfer by cyclic voltammetry and the conductance by conducting mode
atomic force microscopy for PNA duplexes. Both groups found that the charge trans-
port properties of the nucleic acid duplexes that contained one ligand pair in the
presence of transition metal ions are similar to those of non-modified duplexes of
similar length. The conductance of the DNA duplexes increased when multiple
[Cu H 2 ] complexes were incorporated into the DNA duplexes [60].

þ

10.3.2.3 [3 3] Coordination

The octahedral geometry of six-coordinate metal complexes is such that one can antici-
pate unfavorable steric interactions between an octahedral complex used as an alternative
base pair and the adjacent base pairs. Hence octahedral complexes have been pursued
much less than lower coordination number complexes as alternative base pairs. Neverthe-
less in several cases in which pairs of tridentate ligands L have been introduced in DNA
duplexes, it was found that the thermal stability of the duplexes increased significantly in
the presence of transition metal ions. This experimental finding is indicative of the forma-
tion of [M L 2 ] complexes that contribute to the stabilization of the duplex. The finding