ABSTRACT

Acyclic cucurbit[n]uril–β-cyclodextrin chimeric host H1 is presented. The goal of the study is to deepen the cavity of the receptor to allow β-CD complexation of moieties on the guest (especially fentanyl) that protrude from the cavity to enhance binding affinity and deliver new supramolecular antidotes for fentanyl intoxication. ¹H NMR spectroscopy was used to deduce the geometry of the complexes between H1 and H2 and the guest panel whereas isothermal titration calorimetry was used to determine the thermodynamic parameters of complexation. Hosts H1 and H2 retain the essential molecular recognition features of CB[n] receptors, but H1 binds slightly stronger towards the guest panel than H2. Compared to tetraanionic M1 and M2, dianionic H1 and H2 are less potent receptors which reflects the importance of electrostatic interactions in this series of hosts. The work highlights the challenges inherent in the optimisation of binding affinity of hosts as potential supramolecular antidotes.

 抽象的

提出了无环葫芦[n]脲-β-环糊精嵌合宿主H1 。该研究的目标是加深受体的空腔，使β-CD与从空腔突出的客体（尤其是芬太尼）上的部分发生络合，从而增强结合亲和力并提供新的芬太尼中毒超分子解毒剂。 ¹ H NMR 光谱用于推断H1和H2与客体面板之间的络合物的几何形状，而等温滴定量热法用于确定络合的热力学参数。宿主H1和H2保留了 CB[n] 受体的基本分子识别特征，但H1与客体组的结合比H2稍强。与四阴离子M1和M2相比，双阴离子H1和H2是较弱的受体，这反映了静电相互作用在这一系列主体中的重要性。这项工作强调了作为潜在的超分子解毒剂优化宿主结合亲和力所固有的挑战。