Oligomers of α-aminoisobutyric acid (Aib) are achiral peptides that typically adopt 3 10 helical conformations in which enantiomeric left-and right-handed conformers are, necessarily, equally populated. Incorporating a single protected chiral residue at the N-terminus of the peptide leads to induction of a screw-sense preference in the helical chain, which may be quantified (in the form of "helical excess") by NMR spectroscopy. Variation of this residue and its N-terminal protecting group leads to the conclusion that maximal levels of screw-sense preference are induced by bulky chiral tertiary amino acids carrying amide protecting groups or by chiral quaternary amino acids carrying carbamate protecting groups. Tertiary L-amino acids at the N-terminus of the oligomer induce a left-handed screw sense, while quaternary L-amino acids induce a righthanded screw sense. A screw-sense preference may also be induced from the second position of the chain, weakly by tertiary amino acids, and much more powerfully by quaternary amino acids. In this position, the L enantiomers of both families induce a right-handed screw sense. Maximal, and essentially quantitative, control is induced by an L-α-methylvaline residue at both positions 1 and 2 of the chain, carrying an N-terminal carbamate protecting group.

Symmetrical oligourea foldamers were made from meso cyclohexane-1,2-diamine and desymmetrised by incorporating terminal functional groups (carbamates, ureas or thioureas) with differing hydrogen-bonding capacities. Irrespective of solvent, the foldamers populate a dynamic equilibrium of two alternative screw-sense conformers whose relative population is determined by the competing hydrogen-bonding properties of the terminal groups, dictating the foldamer's global hydrogen-bond directionality. Intermolecular association of these dynamic foldamers with achiral anionic guests (acetate or phosphate, but not neutral hydrogen-bonding solvents) leads to inversion of the conformational preference, as strong intermolecular hydrogen bonding induces reorganization of the intramolecular hydrogen-bond network. The foldamers behave as a molecular torsion balance whose conformational preference is governed by competing hydrogen-bond pairing.

Oligoureas (up to n=6) of meso cyclohexane-1,2-diamine were synthesized by chain extension with an enzymatically desymmetrized monomer 2. Despite being achiral, the meso oligomers adopt chiral canonical 2.5-helical conformations, the equally populated enantiomeric screw-sense conformers of which are in slow exchange on the NMR timescale, with a barrier to screw-sense inversion of about 70 kJ mol(-1) . Screw-sense inversion in these helical foldamers is coupled with cyclohexane ring-flipping, and results in a reversal of the directionality of the hydrogen bonding in the helix. The termini of the meso oligomers are enantiotopic, and desymmetrized analogues of the oligoureas with differentially and enantioselectively protected termini display moderate screw-sense preferences. A screw-sense preference may furthermore be induced in the achiral, meso oligoureas by formation of a 1:1 hydrogen-bonded complex with the carboxylate anion of Boc-d-proline. The meso oligoureas are the first examples of hydrogen-bonded foldamers with reversible hydrogen-bond directionality.

The ability of urea-linked oligomers of achiral diamines (achiral analogues of the well-established chiral oligourea foldamers) to adopt helical conformations was explored spectroscopically. Up to four achiral units were ligated either to a well-formed helical trimer or to a single chiral diamine, and the extent to which they adopted a screw-sense preference was determined by NMR and CD. In the best performing cases, a trimeric chiral oligourea and even a single cis-cyclohexanediamine monomer induced folding into a helical conformation.

Oligoureas (up to n = 6) of meso cyclohexane-1,2-diamine were synthesized by chain extension with an enzymatically desymmetrized monomer 2. Despite being achiral, the meso oligomers adopt chiral canonical 2.5-helical conformations, the equally populated enantiomeric screw-sense conformers of which are in slow exchange on the NMR timescale, with a barrier to screw-sense inversion of about 70 kJ mol À1 . Screw-sense inversion in these helical foldamers is coupled with cyclohexane ring-flipping, and results in a reversal of the directionality of the hydrogen bonding in the helix. The termini of the meso oligomers are enantiotopic, and desymmetrized analogues of the oligoureas with differentially and enantioselectively protected termini display moderate screw-sense preferences. A screw-sense preference may furthermore be induced in the achiral, meso oligoureas by formation of a 1:1 hydrogenbonded complex with the carboxylate anion of Boc-d-proline. The meso oligoureas are the first examples of hydrogenbonded foldamers with reversible hydrogen-bond directionality.A helix is a chiral object, [1] but helical molecular structures may be constructed from either chiral or achiral subunits. [2][3][4][5][6] The diastereoisomeric screw sense conformers of helical oligomers built from chiral monomers are necessarily different in energy. As a result, structures such as peptide a-helices (built from l-amino acids) and DNA (built from d-nucleotides) are characterized by a powerful screw sense preference. Helical oligomers of achiral monomers must by contrast populate a left-handed and a right-handed screw-sense conformer of equal energy, which interconvert (enantiomerize) on a timescale characteristic of the type of helix. [7] Examples of such "achiral" helices include polyisocyanates, [8] polyisocyanides, [9] polyphenylenes, [10] and oligomers of the achiral amino acids, whether aromatic, [11,12] quaternary (Aib) [13][14][15] or a,b-didehydro (DPhe). [16] In all these cases, the conformationally averaged monomers have a plane of symmetry that lies parallel to the axis of the helix.An alternative situation arises if a helix is formed from an achiral but meso monomer. In such a case, the monomer has a plane of symmetry perpendicular to the axis of the helix, but no plane of symmetry parallel to the axis. The termini of oligomers of a meso compound are therefore enantiotopic, but become diastereotopic, and therefore chemically inequivalent, on the adoption of a chiral, helical conformation. [17] We set out to investigate the intriguing stereochemical properties and possibilities for molecular communication [7,18] offered by such structures, using as a monomer the meso diamine 1. To retain the meso symmetry of the monomers, these were linked into an oligomer using symmetrical functionality of the urea linkage. Hydrogen-bonded oligoureas built from chiral diamines are a well established class of foldamers, [19][20][21] and the geometry of 1 is compatible with helix formation, [22] even though oligoureas built from achiral d...