Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA.
State Key Laboratory of Systems Medicine for Cancer, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Nat Chem. 2023 Nov;15(11):1559-1568. doi: 10.1038/s41557-023-01315-w. Epub 2023 Oct 9.
The convergent positioning of functional groups in biomacromolecules leads to good binding, catalytic and transport capabilities. Synthetic frameworks capable of convergently locking functional groups with minimized conformational uncertainty-leading to similar properties-are highly desirable but rare. Here we report C5-symmetric aromatic pentaamide macrocycles synthesized in one pot from the corresponding monomers. Their crystal structures reveal a star-shaped, fully constrained backbone that causes ten alternating NH/CH hydrogen-bond donors and five large amide dipoles to orient towards the centre of the macrocycle. With a highly electropositive cavity in a high-energy unbound state, the macrocycles bind anions in a 1:1 stoichiometry in solution, with high affinity for halides and very high affinity for oxoanions. We demonstrate that such macrocycles are able to transport anions across lipid bilayers with a high chloride selectivity and restore the depleted airway surface liquid of cystic fibrosis airway cell cultures.
生物大分子中官能团的汇聚定位导致了良好的结合、催化和传输能力。具有收敛锁定官能团的最小构象不确定性的合成框架，从而导致类似的性质，是非常理想的，但很少见。在这里，我们报告了从相应的单体一锅法合成的 C5 对称芳基五酰胺大环。它们的晶体结构揭示了一个星形的、完全约束的骨架，使十个交替的 NH/CH 氢键供体和五个大酰胺偶极子朝向大环的中心取向。大环在高能非键合状态下具有高度正电性腔，在溶液中以 1:1 的化学计量比与阴离子结合，对卤化物具有高亲和力，对氧阴离子具有非常高的亲和力。我们证明，这种大环能够跨脂质双层转运阴离子，具有高氯化物选择性，并能恢复囊性纤维化气道细胞培养物中耗尽的气道表面液体。
