Homochiral versus Heterochiral Dimeric Helical Foldamer Bundles: Chlorinated‐Solvent‐Dependent Self‐Sorting

Abstract

Aromatic oligoamide sequences programmed to fold into stable helical conformations were designed to display a linear array of hydrogen‐bond donors and acceptors at their surface. Sequences were prepared by solid‐phase synthesis. Solution 1H NMR spectroscopic studies and solid‐state crystallographic structures demonstrated the formation of stable hydrogen‐bond‐mediated dimeric helix bundles that could be either heterochiral (with a P and an M helix) or homochiral (with two P or two M helices). Formation of the hetero‐ or homochiral dimers could be driven quantitatively using different chlorinated solvents—exemplifying a remarkable case of either social or narcissistic chiral self‐sorting or upon imposing absolute handedness to the helices to forbid PM species.

An abiotic, tetrameric, eight-helix bundle

“…34 d) Hydrogen-bonding patterns involving X and P units as observed in a PM (left) and in PP or MM (right) shifted dimers of 3. 38 In a)-d), yellow and red circles around the hydrogen bond donors and acceptors correspond to the yellow cups and red knobs in a) and Figure 3, and to the yellow and red balls in Figure 7.…”

“…Furthermore, removing some of the hydroxy groups through Y->P mutations, as in 3, resulted in the formation of unexpected, shifted parallel † dimers (Figure 2a). 38 The term shifted was used because, in these structure, X units did not face X units of the other helices but were instead shifted by one helix turn and hydrogen-bonded to a P unit. Both PM heterochiral or PP/MM 34 The hexagonal arrangement stems from two X units flanking a Y unit at the surface of a helix, the hydrogen bond donor and acceptor being closer in X than in Y units (Figure 2b).…”

“…However, the fact that they do not occur in the absence of a linker makes them unlikely to happen with a flexible linker that does not impose a particular geometry. 34,38 Parallel PM arrangements were thus also dismissed; (iv) all linkers are too short for PM clockwise tilted arrangements (Figure S8); (iv) the two shorter linkers but not the longer T3-4eg perturb the arrangement of PP counterclockwise tilted arrangements (Figure S9); (v) all linkers seem compatible with PM counterclockwise tilted arrangements albeit in extended conformations unusual for oligoethylene glycols which normally prefer gauche conformations (Figure S10); 48 (vi) all linkers seem compatible with the PP clockwise tilted arrangements (Figure S11). Therefore, at best, two hydrogen-bonded helix-helix arrangements are compatible with the two shorter linkers (PP clockwise and PM counterclockwise tilted arrangements), and three with the longest linker (PP counterclockwise tilted arrangement on top of the former two).…”

“…B and B' thus have an extended conformation with one helix involved in the two-helix domain and the other involved in a three-helix domain, in contrast with A and A', which are back-folded on themselves and are entirely involved in a three-helix domain. The central part of the two helix domain is typical of a head-totail heterochiral (PM) parallel shifted dimer, 38 giving rise to two intermolecular hydrogen bonds (Figures 7c, S43). This arrangement leaves the hydroxy groups of two Y units not involved in hydrogen bonding, the only two in the entire structure (purple balls in Figure 7a,c).…”

“…However, the fact that they do not occur in the absence of a linker makes them unlikely to happen with a exible linker that does not impose a particular geometry. 34,38 Parallel PM arrangements were thus also dismissed; (iv) all linkers are too short for PM clockwise tilted arrangements (Fig. S8 †); (iv) the two shorter linkers but not the longer T3-4eg perturb the arrangement of PP counterclockwise tilted arrangements (Fig.…”