Metal Complexes as Alternative Base Pairs or Triplets in Natural and Synthetic Nucleic Acid Structures - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 357

Zn 2þ ,Ag þ , and Cu 2þ did not affect the T m of the ligand-modified DNA duplex. Interest-
ing from an inorganic chemistry point of view, is the fact that Yang et al. also used a pair
of bidentate ligands or a pair of one bidentate and one tridentate ligands at the end of the
duplex and found that Cu 2þ showed good binding with the mixed ligand environment
while Cu þ showed good binding with the pair of tridentate ligands. Hence the three ligand
environments, bis-tridentate is-bidentate, and tridentate-bidentate, showed selectivity for
specific metal ions.
Bezer et al. synthesized a chiral PNA monomer containing Tpy and used it to create
PNA duplexes with a pair of Tpy ligands in the center or at the end of the PNA duplex
[16d]. They showed that one Cu 2þ ion coordinates to the pair of ligands to form a [Cu
( Tpy ) 2 ] 2þ complex. Although bulky, the complex did not prevent the formation of PNA
duplexes. As expected, the PNA duplex with a terminal metal complex was much more
stable than that with a central complex. A similar [Cu( Tpy ) 2 ] 2þ was formed in 2 0 -amino-
LNA and UNA duplexes by Kalek et al. [18b] and Karlsen et al. [61b], respectively. The
effect of the interstrand metal complexes on the thermal stability of LNA or UNA
duplexes depended on the relative position of the two Tpy ligands with respect to each
other. The effect was smaller in the case of Tpy -containing UNA duplexes than LNA
duplexes because UNA is more flexible than LNA.

10.3.3 Duplexes Containing One Alternative Metal-Ligand Base Pair with
Different Ligands

The metal complexes discussed in the previous section have a pair of identical ligands.
Hence, when they are introduced in two complementary nucleic acid strands, the respec-
tive strands are self-complementary at the level of the metal-containing alternative base
pairs. Metal complexes with two different ligands can function as non self-complemen-
tary, alternative hetero nucleobase pairs. Such complexes with [2 þ 2] or [3 þ 1] coordina-

tion have been incorporated in DNA homoduplexes and in DNA GNA heteroduplexes.

10.3.3.1 [2 þ 2] Coordination

Schlegel et al. have used the bidentate hydroxypyridone and pyridopurine ligands to cre-
ate a Cu 2þ -containing alternative hetero base pair in a GNA duplex (Table 10.1, entry 16)
[53]. Cu 2þ coordination to the hydroxypyridone-pyridopurine hetero base pair caused an
increase of 24 C in the melting temperature of the GNA duplex when compared to the
duplex with the same sequence that had a GNA A T base pair instead of the ligand pair.

þ

10.3.3.2 [3 1] Coordination

A pair of a neutral tridentate ( Pur 2,6-py , Pur 6-bpy ,or Pyr bpy ) ligand and a neutral mono-
dentate pyridine ligand was introduced in the middle of 12-bp DNA duplexes by Switzer
[13d,61a]. The ligand-containing duplexes had a lower melting temperature than the cor-
responding non-modified duplexes (Table 10.1, entries 17-19). Ag þ but not other transi-
tion metal ions restored the stability of the duplexes completely or partly.
The first metal-ligand alternative base pair incorporated in DNA duplexes was of

[3 1] type and was based on tridentate pyridine-2,6-dicarboxylate ( Dipic ) and mono-

dentate pyridine ( Py ) ligands, which were introduced in complementary positions in the
middle of the duplex (Table 10.1, entry 20) [10]. Subsequently, three other tridentate

þ