Chemistry Reference
In-Depth Information
The design of these ligands for the formation of single-stranded helical foldamers relies
on the hypothesis that a combination between square planar metal complexes and a series
of aromatic p-stacking interactions may result in a stable helix [22]. Ligand
1
was
obtained in a five-step synthesis [23,24], with the advantage that the building block com-
pounds can be prepared in multigram quantities and that the amide bond-forming
reactions are straightforward. Metal complexes with Ni
2þ
and Cu
2þ
were prepared in
good yields by mixing
1
with metal acetate precursors. These materials form helical struc-
tures in the solid state, as shown by X-ray diffraction studies, and are conserved in solu-
tion, as evident from NMR spectroscopy.
Circular dichroism (CD) analysis and optical rotation measurements revealed that
the resolved crystalline metal complexes
2a
and
2b
(Figure 11.10) racemize quickly
when dissolved at 5
C. This observation implies that the secondary structure can
reorganize easily and could potentially be used as a template for responsive materi-
als. The secondary structure can also be altered as a consequence of an induced
change in the coordination environment of the metallofoldamers. Indeed, electro-
chemical experiments have shown that structural reorganization occurs upon metal-
centered reduction of Cu
2þ
-containing foldamers. When the reduction is carried out
in the presence of coordinating ligands, it is proposed that apical binding of those
ligands gives square pyramidal complexes. Semi-empirical (AM1) calculations sup-
port the idea that the helical structure can be disrupted by the reduction of Cu
2þ
to
Cu
þ
with concomitant reorganization to a square pyramidal complex. This work is
the first example of abiotic materials in which the metal coordination sphere is not
inherently chiral but instead causes a series of cooperative, non-covalent interactions
that ultimately result in a folded structure. The helical structure is therefore induced
by metal coordination, which is required for folding and further reinforced by aro-
matic p-stacking interactions.
An alternative way to control the chiral environment of a metallofoldamer is via sec-
ondary sphere chirality [25], through which remote stereo-centers control the asymmetric
environment about the metal [26]. In a subsequent study by the same laboratory [27], an
enantiomerically pure oligomeric ligand
3
(Figure 11.11) was synthesized with the
anticipation that it would fold into a discrete conformation upon metal binding, as the
methyl groups positioned on the peripheral benzofuran rings would point to the outside
of the helix [28]. A Ni
2þ
complex was prepared accordingly, crystallized and analyzed by
X-ray diffraction, showing that the helical structure is indeed controlled by the stereo-
centers at the periphery, however, with the peripheral carbonyls pointing to the interior
of the helix. Solution NMR experiments at several temperatures (23 to
40
C) revealed
the existence of two species that undergo chemical exchange, with a barrier of
13 kcal mol
1
.
Further analysis by CD indicated that the complex is a mixture of helices
4(
P
)
and
4(
M
)
with opposite handedness (indicated by the spectrum of
4
, Figure 11.11).
In attempts to control the absolute helicity of the metallofoldamer, a different salophen
(oligomeric ligand
6
, Figure 11.11) was designed to stabilize the (
M
)-helix by a three-
center hydrogen bond [29] while destabilizing the (
P
)-helix through steric interference of
the amide carbonyl by additional ester functions. Accordingly, ligand
6
was synthesized
and mixed with Ni(OAc)
2
to obtain the corresponding Ni-complex (oligomer
5
,Fig-
ure 11.11). As predicted, X-ray diffraction analysis determines the folding of crystalline
5
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