Chemistry Reference
In-Depth Information
duplexes in the presence of transition metal ions is typically indicative of the formation of
a nucleic acid duplex by a combination of hydrogen bonds between nucleobases and coor-
dinative bonds between the metal and the ligands from both strands, as well as p-stacking.
However, the higher strength of coordination bonds compared to that of hydrogen bonds
does not always increase the stability of metal-containing duplexes because the effect of
metal-containing alternative base pairs on the duplexes depends on the geometry and
charge of the metal complex and on the chemical nature and sequence of the nucleic acid.
Achievement of the potential of hybrid metal ion-nucleic acid structures depends on
the ability of researchers to synthesize ligand-containing, nucleic acid oligomers and to
characterize the complexes formed by these oligomers with transition metal ions. The use
of synthetic and characterization methods specific to the fields of coordination and nucleic
acid chemistry creates a concomitant opportunity and challenge. For example, the spec-
troscopic methods used to investigate the stoichiometry and coordination geometry of the
metal complexes attached to nucleic acids may require concentrations exceeding those
typically used or practically achievable for nucleic acid solutions. Also, the new structural
motifs brought about by the stereochemistry of the metal complexes may create alterna-
tive, isomer structures that are close in energy and need to be isolated and characterized.
The incorporation in duplexes of one metal-containing alternative base pair has been
investigated more extensively than that of multiple metal base pairs. In duplexes with
several adjacent ligand pairs, the metal ions can adopt different coordination modes. Fur-
thermore, in the cases of both duplexes with one and with more metal binding sites, the
metal ions can coordinate not only ligands extraneous to the nucleic acid but also nucleo-
bases or phosphate groups. Therefore, to understand the role of the metal ions in the
duplex, one needs to determine the stoichiometry and structure of the metal complex
formed within the duplexes, besides measuring the thermal stability of the duplexes.
Molecular modeling, X-ray and NMR structural studies, and optical and magnetic reso-
nance spectroscopic studies of the metal-containing duplexes can provide information
useful both for the interpretation of the properties of the duplexes and for the rational
design of metal-containing duplexes with specific physical or chemical properties.
An advantage of DNA over artificial, hybrid inorganic-nucleic acid structures is that
DNA can be replicated and amplified. In the last few years, progress has been made
towards the replication and amplification of nucleic acids that can coordinate metal ions.
In 2010, Park
et al.
showed that a DNA polymerase can extend a primed template that had
a TT or CC mismatch at the position corresponding to the 3
0
end of the primer only in the
presence of Hg
2þ
or Ag
þ
, respectively. The dependence of polymerase activity on Hg
2þ
or Ag
þ
was exploited to construct AND, OR, and PASS1 molecular logic gates [40a].
This study showed that the T
Hg
2þ
Ag
þ
C complexes fit in the active site of the
polymerase just like the natural nucleobase pairs do. Shortly before this study, Urata
et al.
showed that a DNA polymerase could incorporate in a primer DNA strand a T nucleobase
opposite a T nucleobase in a DNA template strand in the presence of Hg
2þ
[40b].
The DNA polymerase was able to continue with the full extension of the primer past the
T
T and C
Hg
2þ
T metal-mediated base pair created in the template-extended primer duplex.
The incorporation of the dTTP by the polymerase across the T depended specifically on
Hg
2þ
and could not take place in the presence of dATP.
In the last year, the incorporation of ligands different from the nucleobases C and T by
polymerases in DNA has been also demonstrated. The strategy used by Kalachova
et al.
Search WWH ::
Custom Search