Enhanced Helical Folding of ortho-Phenylenes through the Control of Aromatic Stacking Interactions

The ortho-phenylenes are a simple class of foldamers,
with the formation of helices driven by offset aromatic stacking interactions
parallel to the helical axis. For the majority of reported o-phenylene oligomers, the perfectly folded conformer comprises
perhaps 50–75% of the total population. Given the hundreds
or thousands of possible conformers for even short oligomers, this
distribution represents a substantial bias toward the folded state.
However, “next-generation” o-phenylenes
with better folding properties are needed if these structures are
to be exploited as functional units within more complex architectures.
Here, we report several new series of o-phenylene
oligomers, varying both the nature and orientation of the substituents
on every repeat unit. The conformational behavior was probed using
a combination of NMR spectroscopy, DFT calculations, and X-ray crystallography.
We find that increasing the electron-withdrawing character of the
substituents gives oligomers with substantially improved folding properties.
With moderately electron-withdrawing groups (acetoxy), we observe
>90% of the perfectly folded conformer, and stronger electron withdrawing
groups (triflate, cyano) give oligomers for which misfolded states
are undetectable by NMR. The folding of these oligomers is only weakly
solvent-dependent. General guidelines for the assessment of o-phenylene folding by NMR and UV–vis spectroscopy
are also discussed.

正苯基化合物是一类结构简单的折叠聚合物，其螺旋结构的形成主要由与螺旋轴平行的偏移芳香堆积相互作用所驱动。对于报道的大多数正苯基寡聚物，理想的折叠构象可能占总数的50%至75%。鉴于即使是较短的寡聚物也存在数百甚至数千种可能的构象，这种分布体现了对折叠状态的显著偏差。然而，若要利用这些结构作为更复杂架构中的功能单元，则需要开发具有更优折叠性能的“下一代”正苯基化合物。在本研究中，我们报道了几系列新型正苯基寡聚物，这些寡聚物在每一个重复单元上均改变了取代基的性质和取向。通过核磁共振波谱、密度泛函理论计算和X射线晶体学相结合的方法，对构象行为进行了探究。我们发现，增加取代基的吸电子特性可显著提升寡聚物的折叠性能。使用中等吸电子基团（乙酰氧基）时，观察到超过90%的理想折叠构象，而使用更强的吸电子基团（三氟甲酸基、氰基）的寡聚物，其错折叠状态在核磁共振波谱中无法检测到。这些寡聚物的折叠性质对溶剂的依赖性较弱。此外，还讨论了利用核磁共振波谱和紫外-可见光谱评估正苯基折叠的一般性指南。