Metal Complexes as Alternative Base Pairs or Triplets in Natural and Synthetic Nucleic Acid Structures - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 341

Figure 10.6 Alternative base pairs based on two-coordinate metal complexes.

(see also Section 10.4). In the absence of metal ions, the 17-bp oligonucleotide d(A 7 Tri-
azole 3 T 7 ) formed a hairpin structure. In the presence of Ag þ , the same oligonucleotide
formed a duplex with a palindromic sequence, in which three central metal-containing,
alternative base pairs [ Triazole .Ag. Triazole ] were flanked by AT base pairs [44]. The
structural change from hairpin to duplex induced by Ag þ was demonstrated by using a
combination of Ultraviolet (UV), circular dichroism (CD), and fluorescence spectroscopy,
MALDI-ToF mass spectrometry, and dynamic light scattering. The Imidazole -containing
duplex has been characterized by X-ray crystallography (see Section 10.4) [45].
The stability constant of complexes formed between Ag þ and pyridine is such that a
[Ag( Py ) 2 ] þ complex does not form in aqueous solutions containing micromolar concen-
trations of Ag þ and Py [46]. Nevertheless, in the same concentration range, a [Ag( Py ) 2 ] þ
complex formed within DNA duplexes that contained a pair of Pys in complementary
positions, which can be attributed to a duplex-induced, supramolecular chelate effect
(Table 10.1, entry 1) [12b,47]. The coordination of one equivalent of Ag þ to the pair of
Py was confirmed by 1 H-NMR titrations, which showed that the Ag þ binding affected
exclusively the protons of Pys and not those of the natural nucleobases. Ag þ coordination
to Py had a stabilization effect on the modified DNA duplexes that depended on the
sequence and length of the DNA duplex. For example, Ag þ had no effect on the stability
of a Py -modified DNA duplex that had 15 bp [47] but increased the stability of the same
type of duplex that had a different sequence and 21 bps (Table 10.1, entry 1) [12b]. The
stabilization effect of Ag þ on the latter duplex increased with the Ag þ concentration and
was largest in the presence of three equivalents of Ag þ .

10.3.2.2 [2 þ 2] Coordination

Several groups have developed metal-based alternative base pairs with [2 2] coordina-

tion by using the bidentate ligands such as bipyridine, 8-hydroxyquinoline, hydroxypyri-
done, or salicylaldehyde. Salen , a four-dentate ligand that coordinates to metal ions
through two nitrogen and two oxygen atoms, is also included in this section because of
the similarity between its coordination complexes and those with bis(salicyladehyde)
coordination. This ligand was created by metal-templated reaction of salicyladehyde lig-
ands incorporated in DNA with bis-amines.

þ

N,N-Coordinating Ligands: Bipyridine and Related Aromatic Bis-Imine
Ligands. 2,2 0 -Bipyridine ( Bpy ) has a high affinity for a variety of transition metal ions
[46,48] and can participate in p-stacking interactions. Hence, this ligand was one of the
first ones used to create metal-binding sites in nucleic acids (Figure 10.7). For incorpora-
tion in ss DNA, Bpy has been connected at its 5-position to the 1 0 position of the 2 0 -
deoxy- D -ribose, either directly [49] or through a methylene linker [11b]. (Table 10.1,