Artificial DNA Directed toward Synthetic Metallofoldamers - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 315

same length give different melting points. In particular, GC-rich duplexes have higher
melting points than AT-rich sequences due to the higher stability of the triply hydrogen-
bonded G-C base pairs. The same may be observed for DNA sequences containing one or
several Watson-Crick base pairs replaced by pairs of artificial nucleobases. When the
modified base pairs have a higher stability than the natural ones, the melting point rises,
whereas when they contribute less to the attractive interaction between the strands, the
melting point decreases. Concerning the topic of metal base pairing, it is instructive to
compare the melting points of a metal base pair containing a double strand (Figure 9.8b),
a ligand containing a double strand in the absence of metal ions (Figure 9.8c) and a dou-
ble strand containing a Watson-Crick base pair at the same position (Figure 9.8d).
Whereas the oppositely arranged ligands usually form a destabilizing mismatch in the
absence of metal ions (with a melting point lower than the duplex containing the Watson-
Crick base pair), the addition of a suitable metal ion results in a significant increase in
melting temperature, often exceeding the value obtained from the unmodified DNA
sequence.
In cases where the coordination of the metal ions to the ligand-containing DNA
duplexes gives rise to other spectroscopically observable features such as color change,
fluorescence or changes in circular dichroism, the respective spectroscopic changes may
be monitored in dependence of the amount of metal added and/or change in temperature.
Furthermore, the interaction of the double strands with the metal ions may be studied by
HPLC, gel electrophoresis, EPR and NMR spectroscopic methods.
9.4.3 X-Ray Structure Determination
Single-crystal X-ray structure determination usually yields the best structural description
of a coordination compound in terms of connectivity, bond distances, angles and stereo-
chemical relationships. In the case of metal-containing oligonucleotide duplexes, how-
ever, the growing of suitable single crystals and the interpretation of diffraction data is
often a time- and material-consuming process requiring a good bit of luck. So far, only a
limited number of crystal structures of oligonucleotides containing metal base pairs have
been reported. Figure 9.9 shows two structures reported in the literature. The first struc-
ture contains two isolated asymmetric metal base pairs consisting of one tridentate pyri-
dine-2,6-dicarboxylate (Dipic) ligand and one monodentate pyridine ligand coordinating
a Cu(II) ion in a square-planar geometry (Figure 9.9a and b) [37]. Interestingly, the palin-
dromic dodecamer forms a Z-type, left-handed helical structure, a fact that seems to be
controlled by the requirement of the Cu(II) ions adopting a Jahn-Teller distorted octahe-
dral coordination environment in which the O6 of the neighboring guanine base on one
side of the metal base pair and the ribose O4 0 of a thymine on the other side coordinate
the Cu(II) ion in its apical positions (dashed lines in Figure 9.9a). Especially the latter
coordination of the backbone sugar to the two metal centers contained in the dodecamer
sequence seems to have such a strong influence on the whole duplex conformation, lead-
ing to a nearly perfect Z-DNA-type structure.
Figure 9.9c shows another example, where two Cu(II)-mediated base pairs based on the
hydroxypyridone ligand are incorporated into an artificial duplex consisting of an open
chain propylene glycol backbone [38]. The main intention of incorporating the metal
base pairs into this construct actually was their positive effect on duplex stability in order