Helicogenicity of solvents in the conformational equilibrium of oligo(m-phenylene ethynylene)s: implications for foldamer research

Abstract

A (R)-binaphthol tethered bis-hexameric oligo(m-phenylene ethynylene) foldamer was examined in 30 solvents to correlate the unfolded-folded conformational equilibrium to bulk solvent properties and specific solvent-chain interactions. The oligomer is soluble in a variety of solvents of intermediate polarity, with the majority of these solvents being helicogenic. The amphiphilic nature of the chain allows the solvophobic backbone to be solubilized in a wide range of solvents through the polar triethylene glycol side chains. As demonstrated through UV and CD spectroscopic experiments, the helical conformation is increasingly stabilized with increasing solvent polarity in the absence of specific solvent-chain interactions. Surprisingly, very few solvents are capable of fully denaturing the helix, indicating the strength of the solvophobic driving forces in this cooperative system. The folding reaction for this amphiphilic oligomer can be described as a compromise in solubility properties, where chains collapse intramolecularly into helical conformations to minimize solvent-backbone contacts while maintaining favorable solvent-side chain interactions for solvation. In terms of mimicking the properties of biomacromolecules, foldamers using solvophobic driving forces must be tempered with functionalities that promote solubility of the folded state while at the same time allowing access to the unfolded state through the use of denaturants.

Figure 1

The chemical structure of 1: a bis-hexameric phenylene ethynylene tethered through (R)-binaphthol (Inset); the side chains promote solubility in a wide range of solvents. The solvent-dependent folding reaction of 1: the unfolded state contains both transoid and cisoid backbone conformations, which become all-cisoid in the folded state. The result is a helical conformation stabilized by intramolecular aromatic–aromatic contacts whose strength is modulated by solvent. The (R)-binaphthol moiety induces a twist sense bias in the resulting helix. Side chains have been omitted for clarity. The helical conformation shown is an energy minimized structure.^§

Figure 2

UV absorption and CD spectra of 1 (3.0⋅10⁻⁶ M at ambient temperature) in CHCl₃ (solid) and CH₃CN (dashed).

Figure 3

UV absorption ratios (A₃₁₃/A₂₉₅) of 1 from Table 1 (ranging from CCl₄ to CH₃CN). The linear fit [excluding data from the three chlorohydrocarbon (Δ) solvents] provided the following relationship: A₃₁₃/A₂₉₅ = 0.834–0.259⋅E.

Figure 4

CD intensities at Δɛ₃₂₂ of 1 from Table 1 (ranging from CCl₄ to CH₃CN). The linear fit [excluding data from the three chlorohydrocarbon (Δ) solvents] provided the following relationship: Δɛ₃₂₂ = −167.5–3,121⋅E.