Artificial DNA Directed toward Synthetic Metallofoldamers - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 319

Figure 9.13 Synthesis of the C -glycosidic salicylic aldehyde base (a precursor to the salen
ligand) and its phosphoramidite.

large number of transition metal ions in a square-planar, square-pyramidal or octahedral
fashion [50]. The direct precursor of the ligand is a salicylic aldehyde, which reacts with
ethylenediamine to the tetradentate ligand. Such a salicylic aldehyde, intended to be
incorporated into DNA as a C -nucleoside, was prepared according to Figure 9.13 carrying
a silyl protecting group on the phenolic hydroxyl group and having its aldehyde function-
ality masked as a cyclic acetal.
After DNA synthesis and the removal of all protecting groups, salicylic aldehyde
containing single strands of matching sequence were hybridized and ethylenediamine
was added in excess in order to form the salen ligand as a covalent cross-link between
the strands. Since the formed imine bonds are not stable in the aqueous medium used,
the salen ligand forms and reopens again in a dynamic equilibrium which can be seen
by the relatively small increase in melting temperature ( 5 K) upon the addition of

ethylenediamine to the duplex. This situation changes dramatically when one equiva-
lent of transition metal ions is added: the metal coordinates inside the tetradentate
salenligandwithahighaffinityandthereby stabilizes the ligand's imine bonds
against hydrolytic cleavage. Consequently, the covalent cross-link conveys a tremen-
dous thermal stability to the double helix. In the case of Cu(II), the increase in melting
temperature was found to be larger than 40 K, which is the largest duplex stabilization
achieved by metal base pairing so far [50].
In accordance with the metal stacking experiments using the hydroxypyridone base pair
discussed in Section 9.5.2, the salen base pair was also used to produce arrays of stacked
metal ions inside the DNA double helix (Figure 9.14). By incorporating ten consecutive
ligands, metal stacks spanning one entire helical twist (considering a B-DNA type struc-
ture) were generated using transition metal ions such as Cu(II) and Mn(II) (which is
oxidized to Mn(III) upon complexation) [51]. Interestingly, the weaker bound Mn(II) ions
gave better results in terms of uniformity and purity of the formed metallated double
helices, most likely attributed to the “self-healing” of preliminary formed, kinetically
misfolded products into the perfectly stacked array of ten metal base pairs as the thermo-
dynamically most stable product (Figure 9.15a).
In an attempt to introduce even more complexity into the system, a second metal base
pairing system orthogonal to the first one was introduced into the same double helix in
order to create mixed metal arrays of predetermined sequence inside the double helix
(Figure 9.15b) [49]. Therefore, the salen-Cu(II) base pair was combined with the non-

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