Synthesis, Structure, and Binding Properties of Lipophilic Cavitands Based on a Calix[4]pyrrole-Resorcinarene Hybrid Scaffold

We report the synthesis, structural
characterization, and binding
properties of a series of unprecedented cavitands based on a meso-dodecyl-calix­[4]­pyrrole-resorcin­[4]­arene hybrid scaffold.
The reported structural and conformational features of the prepared
cavitands are derived from results obtained in solution, solid state,
and molecular modeling studies. In the solid state, these cavitands
are exclusively observed in the kite C4 structure and as a racemic mixture of two cyclochiral conformers,
which are interconverting fast on the 1H NMR time scale,
according to solution studies. In agreement, molecular modeling studies
assign an energy preference for the kite conformer of the cavitands.
The polar interior of the synthesized containers allows for the inclusion
of a series of pyridine N-oxide derivatives. This
results in the formation of 1:1 complexes that are kinetically and
thermodynamically highly stable. The putative switching process between
the vase and kite forms of these cavitands is investigated in solution
by means of variable temperature 1H NMR experiments. N-Oxide guests that are size and shape complementary to
the volume of the cavity of the vase form are also employed to facilitate
its emergence. All of the results obtained indicate the existence
of a remarkable preference toward the kite conformation both in free
and bound calix[4]­pyrrole-based cavitands.

本工作报道了一系列基于中位十二烷基杯[4]吡咯（calix[4]pyrrole）-间苯二酚[4]芳烃（resorcin[4]arene）杂合骨架的新型穴番（cavitand）的合成、结构表征与结合性能。所制备穴番的结构与构象特征，均来源于溶液态、固态及分子模拟研究的实验结果。固态研究显示，此类穴番仅以风筝状C4对称结构存在，且为两种环手性构象体的外消旋混合物；根据溶液态研究结果，这两种构象体在氢核磁共振（1H NMR）的时间尺度上可快速相互转化。与之相符的是，分子模拟研究证实，该类穴番的风筝状构象体具有能量优势。该合成所得穴状容器的极性内腔，可容纳一系列吡啶氮氧化物衍生物。此过程可形成动力学与热力学稳定性均极为优异的1:1主客体配合物。本研究通过变温氢核磁共振实验，在溶液体系中探究了此类穴番的花瓶状与风筝状构象间的潜在转换过程。同时，我们还选用了尺寸与形状与花瓶状构象空腔体积互补的吡啶氮氧化物客体，以促进花瓶状构象的显现。所有实验结果均表明，无论是游离态还是结合态的杯[4]吡咯类穴番，均表现出对风筝状构象的显著偏好。