Metal Complexes as Alternative Base Pairs or Triplets in Natural and Synthetic Nucleic Acid Structures - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 353

This effect is similar to that in which polytopic ligands form complexes more stable
than the corresponding complexes with individual ligands.
On the other hand, steric constraints such as those exerted on the ligand position
by the duplex or by the way in which the ligand is attached to the PNA backbone
limit the supramolecular effect. In other words, the relative orientation of the ligands
within the PNA duplex may disfavor the formation of a metal complex. Indeed, a
PNA duplex that contained Q ligands attached to the backbone through the ortho
position to the imine nitrogen of the ligand formed [Cu Q 2 ] complexes with stability
constant lower than that of [Cu Q 2 ] complexes with Q ligands in solution [16e].
The structure of GNA or fully complementary PNA duplexes as probed by CD
spectroscopy was not affected by the presence in the duplex of a [Cu Q 2 ]complex
[16b,17b]. Partly complementary PNA duplexes did not show a CD spectrum in the
absence or in the presence of Cu 2þ , suggesting that the mismatches prevent the
transmission of the chiral induction effect of the L -lysines situated at the C-terminus
of the PNA strands. Nevertheless, the EPR spectra of the Q -PNA duplexes formed
from partly complementary strands were similar to each other and to the spectrum
of the fully complementary Q -PNA duplex [16b], and confirmed the coordination of
two Q ligands to Cu 2þ . This observation suggests a similarity in the environment of
the duplexes around the [Cu Q 2 ] complexes irrespective of the degree of complemen-
tarity of the two strands that form the duplex.
Schiff bases are very versatile ligands and have high affinity for metal ions. The
N,N 0 -bis(salicylidene)ethylendiamine or salen ( Salen ) version is widely used for its
catalytic properties. Salen formation from salicylaldehyde ( Sal ) and ethylenediamine
is a reversible process and the coordination of metal ions is generally required as a
driving force for the reaction to occur in aqueous environment. The preorganization
of an aldehyde and an amine close to each other onto a template entropically favors
the formation of the condensation product in dilute samples, a strategy used early on
in Inorganic Chemistry to form Salen complexes. In 1997, a ss DNA template was
used to support the condensation of a 3 0 -end aldehyde group with the 5 0 -end amino
group of two different, shorter ss DNA that were complementary to adjacent portions
of the DNA template [55]. In a related approach, Czlapinski and Sheppard showed
the formation in presence of ethylenediamine but in the absence of a metal ion of a
non-metallated Salen between two salicylaldehydes situated at the end of opposite
strands in a 15-bp DNA duplex [56]. The two salicylaldehyde ligands were linked
directly to the terminal phosphate group of each strand rather than to a sugar moiety
and were likely to p-stack with the nucleobase pairs in a manner similar to that in
which overhang nucleobases stack at the end of a nucleic acid duplex. The reversible
formation of a non-metallated form of Salen was invoked to explain the hysteresis
observed in the presence of ethylenediamine in the melting of a DNA duplex that
contained two salicyladehydes in central, complementary positions [15d].
Usually, the two aromatic rings of Salen in coordination complexes are coplanar.
Hence Salen bears structural similarity to a nucleobase pair and it can participate in p-p
interactions with adjacent nucleobase pairs. This compatibility between the Salen ligands
and their metal complexes with the base pairs in the DNA duplex is supported by the
results of CD studies. Room temperature CD spectra of DNA duplexes that contained a
central of terminal pair of salicylaldehyde ligands and formed a M 2þ - Salen complex in