Introduction to Unnatural Foldamers - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 70

3 -
h Phg-OBn, as the hydrogen bonding pattern in the crystal lattice shows the formation of
infinite parallel b-sheets running along the a axis, as previously observed for Boc- L -Phe-
D -Oxd-OBn. Thus, the reversal of the absolute configuration of the stereogenic center of
the h Phg moiety ends in a dramatic variation of the preferential conformation of the two
compounds, which in turn induces a different crystal packing and consequently a different
crystal morphology.
The synthetic approach to supramolecular materials of foldamers containing the
4-carboxy oxazolidin-2-one unit or related molecules is highly tunable with endless varia-
tions, so, simply by changing the design and the synthesis, a wide variety of foldamers
with the required properties may be prepared “on demand.”

A completely different packing was observed for epimer Boc- L -Phe- D -Oxd-( R )-b

2.3 Abiotic Foldamers

The potential usefulness of a particular class of foldamer in the design of secondary
and tertiary structural motifs depends much on the predictability of their folding.
Biotic (both homogeneous and hybrid) foldamers are mainly constituted of aliphatic
chains that may assume a wide variety of conformations, as we have just shown. To
overcome this problem, several groups in recent years envisaged the synthesis of
oligomers containing rigid scaffolds, such as aromatic rings. Following this method,
predictability is associated with the structure itself, which can be designed to have
no choice but to fold in a desired conformation. These foldamers containing several
aromatic rings are very different from natural oligomers and were recently defined
“abiotic” by Huc and Guichard [6]. These compounds are generally easy to prepare
and have very stable secondary structures. This is a very important feature, as ter-
tiary structures are hard to build using unstable secondary building blocks. Several
reviews recently reported the synthesis and applications of aromatic foldamers [73].
We will present here a short overview of their general structures and explain in Sec-
tion 2.4 how they get organized in the presence of external agents.
Depending on the primary driving force for folding, these unnatural aromatic oligomers
can be classified into two main categories, although there are a number of cases where a
combination of both applies: (a) molecules that fold because of hydrogen bonding prefer-
ences built into the repeat units and (b) those in which folding is primarily driven by sol-
vophobic or aromatic interactions. There is no need to explore the conformational space
accessible to the entire molecule to determine its most stable conformation since it pri-
marily results from local conformational preferences. Taking as an illustration the Ram-
achandran plots used to map the torsion angles corresponding to stable folded
conformations in peptides, the experimentally encountered values for the torsion angles
in fully predictable foldamers are reduced to very small areas [5].
In hydrogen-bonded aromatic foldamers, the folding process is dependent on preorga-
nization due to hydrogen bond donor and acceptor units that have been deliberately intro-
duced to favor certain conformations. Folding usually requires a nonpolar solvent like
chloroform, which does not disrupt this hydrogen-bonding pattern. Based on the hydrogen
bond donor and acceptor functionality, these can be further divided into two categories:
ones in which the aromatic rings are connected through amide bonds (i.e., oligoamides)