Photoresponsive Helical Foldamers: Conformational Control Through Double Helix Formation and Light-Induced Protonation

Abstract

Helical foldamers constitute particularly relevant targets in the field of host-guest chemistry, be that as hosts or substrates. In this context, the strategies reported so far to control the dimensions and shape of foldamers mainly involve modifications of the skeleton through covalent synthesis. Herein, we prepared an oligopyridine dicarboxamide foldamer substituted by photo-active tetraphenylethylene units (TPE). We demonstrate that it is possible to toggle the length of a helical foldamer by two means. First, the elongation of foldamers can be tuned by adjusting the concentration, as demonstrated by DOSY NMR spectroscopy and X-ray diffraction analyses on both the single and the double helix structures. Secondly, and in a more original manner, a photo-induced protonation process triggered by TPE units promotes a novel pathway to unfold helical foldamers, leading to dramatic conformational and spectroscopic changes.

Keywords: Helical foldamers; conformational control; double helix formation; photoinduced process; tetraphenylethylene.

Scheme 1

Chemical structure of target foldamer A.

Scheme 2

Synthetic scheme leading to foldamer A and reference 5.

Figure 1

Crystallographic structures (Movie S1) of foldamer A as a single helix ((a), M configuration) and as a double helix ((b) P,P configuration) and the corresponding cylinders dimensions as extracted from DOSY NMR. Solvent molecules and isobutoxy chains are omitted for clarity.

Figure 2

¹H NMR spectra of foldamer A at 0.3 mM and 42 mM (CDCl₃, 298 K, 500 MHz) and the corresponding DOSY NMR spectra recorded in the same conditions (42 mM). Minor variations of chemical shifts result from intermolecular contacts.

Figure 3

Evolutions of absorption (a) and emission (b) spectra of foldamer A under UV‐ irradiation (313 nm) (red line=before irradiation, blue line=after irradiation), CHCl₃, C=2.5×10⁻⁵ mol.L⁻¹, l=1 cm, λ_exc=309 nm.

Scheme 3

a) Photocyclization‐oxidation process represented in the case of 5. b) Synthesis of N‐oxide 7.

Figure 4

Normalized absorption spectra of foldamer A before (red curve), after irradiation (blue curve), after protonation (purple, 80 eq. of TFA) after irradiation and addition of triethylamine (black, 20 eq.) CHCl₃, C=2.5×10⁻⁵ mol.L⁻¹, l=1 cm, λ_exc=309 nm.

Figure 5

(a) Evolution of the CD spectra of foldamer A (CHCl₃, C=3×10⁻⁵ mol.L⁻¹), l=1 cm) in the presence of (R)‐mandelic acid (200 equivalents) and upon continuous irradiation (313 nm). b) Optimized geometry of partially protonated foldamer A calculated through molecular mechanics (MM+). Hydrogen bonds responsible for the unfolding process in dotted lines.

Figure 6

Shape adjustments through double helix formation or unfolding processes of an helicoidal foldamer.