Directing the Self-Assembly of Aromatic Foldamer Helices using Acridine Appendages and Metal Coordination

Abstract

Folded molecules provide complex interaction interfaces amenable to sophisticated self-assembly motifs. Because of their high conformational stability, aromatic foldamers constitute suitable candidates for the rational elaboration of self-assembled architectures. Several multiturn helical aromatic oligoamides have been synthesized that possess arrays of acridine appendages pointing in one or two directions. The acridine units were shown to direct self-assembly in the solid state via aromatic stacking leading to recurrent helix-helix association patterns under the form of discrete dimers or extended arrays. In the presence of Pd(II), metal coordination of the acridine units overwhelms other forces and generates new metal-mediated multihelical self-assemblies, including macrocycles. These observations demonstrate simple access to different types of foldamer-containing architectures, ranging from discrete objects to 1D and, by extension, 2D and 3D arrays.

Keywords: aromatic stacking; foldamer; helical conformation; metal coordination; self-assembly.

Figure 1

Foldamer sequences with acridine appendages and expected interactions. a) Chemical structures of units Q^a and Q. Interactions enabled by the acridine group: π‐π and dipole‐dipole interactions (b), and metal coordination with Pd(II) (c). Sequences of foldamers with acridine groups on one side of the helix (d) and two neighboring sides of the helix (e). Schematic top and side views indicate the positions of acridine units on helices.

Figure 2

300 MHz ¹H NMR spectra of 1 c (a), 1 b (b) and 1 a (c) in CDCl₃. Stars indicate signals belonging to acridine moieties. Different views of the crystal structures of 1 b (d–h) and 1 c (i–m). Hydrogen atoms, isobutyl groups, and solvent molecules are omitted for clarity. Arrows indicate the N‐to‐C helix orientation. Acridine groups are shown in space filling representation in (d–f) and (i–k). Intramolecular and intermolecular average distances from the atoms of acridine groups to the aromatic planes are indicated in h) and m), respectively.

Figure 3

300 MHz ¹H NMR spectra of oligomers of 2 c (a), 2 b (b) and 2 a (c) in CDCl₃. Stars indicate signals belonging to acridine moieties. (d–i) Different views of the crystal structure of 2 b. Hydrogen atoms, isobutyl groups and solvent molecules, are omitted for clarity. Angles between acridine moieties and the helix are indicated in d) and e). Acridine moieties are shown as space‐filling models in g–i).

Figure 4

The assembly of 2 b in the solid state. Top view (a) and side view (b) of one dimensional continuous ladder organization of P and M helices mediated by stacking between acridine units. Acr1 and acr3 are shown in red and acr2 is shown in blue, all in space filling representation. In a), arrows indicate N‐to‐C helix orientation. In b), black circles and white circles indicate that the C‐terminus or the N‐terminus of the helix is visible, respectively. (c, e and g) show different views of helix‐helix interface B and (d, f, and g) show the same views of helix‐helix interface B. In (c–h), acr units borne by the M helix are shown in green, and acr units borne by the P helix are shown in gold. Acr units are shown either in tube representation (g, h) or in space‐filling representation (c–f). Average distances from atoms of acridine rings to the close aromatic planes are indicated in (g and h). Hydrogen atoms, isobutyl groups and solvent molecules, are omitted for clarity.

Figure 5

A model to show the interconversion between PP/PM/MM helices connected with a single metal coordination (a). Formation of complex Pd(1 a)₂Cl₂ followed by NMR spectroscopy (300 MHz, CDCl₃) at different time intervals after mixing PdCl₂(CH₃CN)₂ with two equiv. of 1 a (b–e). Different views of the crystal structure of Pd(1 a)₂Cl₂ (f–h). In (f), arrows indicate N‐to‐C helix orientation. In (g and h), the side views of two inequivalent complexes found in the asymmetric unit are shown and the distinct helix‐helix orientation indicated. Hydrogen atoms, isobutyl groups and solvent molecules, are omitted for clarity.

Figure 6

The ¹H NMR (300 MHz) spectra of 1 b (c) and its complex with palladium Pd₂(1 b)₂Cl₄ containing four isomers (b) as well as one of the isomers purified (a) in CDCl₃, (d–h) the crystal structure of the complex Pd₂(1 b)₂Cl₄ showing different views, d) front view, e) top view through the helices; f) side view showing the angle of acridine to the axis of helix; g) side view with the angle of palladium atoms to the axis of helices; h) views of the palladium coordination. One dimensional solvent channel formed by the stacking of the complex Pd₂(1 b)₂Cl₄, on the view from (i) b‐axis and (j) c‐axis. All the hydrogen atoms (d–j) and side chains (d–h) in the crystal structures are removed for clarity.