Controlling Dipole Orientation through Curvature: Aromatic Foldamer Bent β‑Sheets and Helix–Sheet–Helix Architectures

The
helix, turn, and β-strand motifs of biopolymer folded
structures have been found to prevail also in non-natural backbones.
In contrast, foldamers with aryl rings in their main chains possess
distinct conformations that may give access to folded objects beyond
the reach of peptidic and nucleotidic backbones. In search of such
original architectures, we have explored the effect of bending aromatic
amide β-sheets using building blocks that impart curvature.
Cyclic and multiturn noncyclic sequences were synthesized, and their
structures were characterized in solution and in the solid state.
Stable bent-sheet conformations were shown to prevail in chlorinated
solvents. In these structures, folding overcomes intramolecular electrostatic
repulsions and forces local dipoles in each layer of the stacked strands
to align in a parallel fashion. Sequences having helical segments
flanking a central bent aromatic β-sheet were then synthesized
and shown to form well-defined helix–turn–helix architectures
in which helical and sheet subcomponents conserve their respective
integrity. These objects have a unique basket shape; they possess
a cavity the depth and width of which reflects the curvature of the
β-sheet segment. They can be compared to previously described
helical closed-shell receptors in which a window has been open, thus
providing a means to control guest binding and release pathways and
kinetics. As a proof of concept, guest binding to one of the helix–sheet–helix
structures is indeed found to be fast on the NMR time scale while
it is generally slow in the case of helical capsules.

生物聚合物折叠结构中的螺旋（helix）基序、转角（turn）基序与β链（β-strand）基序，同样普遍存在于非天然主链体系中。与之相对，主链含芳环的折叠体（foldamer）具有独特构象，有望获得肽主链与核苷酸主链无法企及的折叠结构。为探索这类新颖结构，我们采用可赋予曲率的结构单元，对芳族酰胺β折叠片的弯曲效应展开了研究。我们合成了环状序列与多匝非环状序列，并在溶液及固态下对其结构进行了表征。研究表明，稳定的弯曲折叠片构象在氯化溶剂中占主导。此类折叠结构中，折叠作用克服了分子内静电排斥，使堆叠链各层的局部偶极以平行方式排布。随后我们合成了侧翼带有螺旋区段的中心弯曲芳族β折叠片序列，结果显示其可形成定义明确的螺旋-转角-螺旋（helix–turn–helix）结构，其中螺旋与折叠片亚组分各自保持结构完整性。这类结构具有独特的篮状外形，其空腔的深度与宽度与β折叠片区段的曲率相对应。该结构可与此前报道的开有窗口的螺旋闭合壳受体相类比，为调控客体结合、释放途径及动力学提供了可行手段。作为概念验证，我们发现客体与其中一种螺旋-折叠片-螺旋结构的结合在核磁共振（NMR）时间尺度上表现为快速结合，而在螺旋胶囊体体系中通常为慢速结合。