Metal Complexes as Alternative Base Pairs or Triplets in Natural and Synthetic Nucleic Acid Structures - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 359

While Cu 2þ coordination increased the Dipic Py duplex stability, the addition of Ce 3þ ,
Mn 2þ ,Fe 2þ ,Co 2þ ,Ni 2þ ,Zn 2þ ,Pd 2þ ,orPt 2þ had no effect.
2,2 0 -Dipicolylamine ( DPA ) is a tridentate ligand that has been introduced in ss LNA
(attached to the 2 0 -NH backbone group), ss PNA (attached to the NH 2 end of the PNA) or
ss GNA (attached to the backbone methylene group) (Figure 10.4) [17a,18a,67]. In the
GNA

DNA duplexes, DPA was situated across a monodentate ligand Imidazole , Tria-
zole ,or Tetrazole [17a]. In the absence of transition metal ions, the DPA -modified
GNA DNA duplexes had a thermal stability lower than that of the non-modified

GNA DNA duplexes and independent of the nature of the monodentate ligand [17a]. In

the DPA -modified LNA DNA duplexes, DPA did not have an extraneous group in the

complementary position. These duplexes had a thermal stability higher than that of the
non-modified LNA DNA duplexes [18a]. This effect is opposite to that observed for lig-

and-modified DNA duplexes, which are typically less stable than their non-modified
counterparts, but is similar to that observed for LNA

DNA duplexes containing aromatic

substituents at the 2 0 -NH group [68].
DPA was shown to form [3 1] metal-based alternative base pairs in three types of

nucleic acid duplexes. When the DPA -containing ss LNA and ss PNA formed hetero-
duplexes with DNA, a transition metal ion could coordinate the tridentate ligand together
with a monodentate phosphate group from the opposite DNA strand. Ni 2þ ,Cu 2þ ,and
Zn 2þ were shown to coordinate to one or two DPA ligands situated within an LNA

þ

LNA
duplex and stabilize the duplexes (Table 10.1, entry 24). In most cases, the addition of
more than one equivalent of metal ion per pair of adjacent DPA ligands destabilized the
duplex, suggesting that steric and electrostatic repulsion occur when each of the DPA
ligands binds a metal ion (Table 10.1, entry 24). In the GNA

DNA duplexes, DPA was
situated across a monodentate ligand Imidazole , Triazole ,or Tetrazole [17a]. In the
presence of Ag þ , the melting temperature of these duplexes increased when compared to
the T m of the ligand-modified duplexes in the absence of the metal ions, but not with
respect to the non-modified duplexes (Table 10.1, entries 25-27). The increase in T m cor-
related with the basicity of the mononuclear azole group.
Molecular modeling and DFT calculations on DPA -modified LNA DNA duplexes sup-

1] DPA -M 2þ -PO 4 3 coordination mode can be realized by
coordination of a DPA ligand from one strand and a phosphodiester from either the same
strand or from the opposite strand of the LNA

ported the fact that a [3 þ

DNA duplex [18a]. This coordination
model is compatible with the data obtained for DPA -modified PNA DNA duplexes,

namely that: (a) the stability of a Ni 2þ -containing, DPA -modified PNA DNA duplex did

not depend on the duplex sequence, and (b) the effect of Ni 2þ on the duplex stability
depended on the ionic strength of the solution [67]. In the case of LNA

DNA duplexes
that contained two or more DPA ligands, theoretical studies showed that one transition
metal ion can coordinate two DPA ligands from opposite strands to form either a mono-
nuclear or dinuclear complex that acted as a crosslink between the two strands [69].

10.4 Duplexes Containing Multiple Metal Complexes

Duplexes or triplexes that contain several metal-containing alternative base pairs entry
point in the synthesis of homo- and hetero-metal polynuclear clusters within nucleic acid