浙江大学孔学谦研究小组揭示药物在金属有机框架中的缺陷辅助装载和对接构象。该研究于2021年1月5日在线发表于国际一流学术期刊《德国应用化学》。

研究人员发现金属有机框架（MOF）的缺陷在许多带有磷酸或膦酸基团的药物的装载中起着关键作用。主体/客体之间的相互作用以磷酸/膦酸基团和缺陷位点之间的库仑吸引作用为主导，并且极大地增强了负载能力。对于没有磷酸/膦酸基团的类似分子，或者对于没有缺陷的MOF，其负载能力会大大降低。

研究人员采用了固态核磁共振（NMR）和分子模拟来阐明药物-载体相互作用的机制。通过实验和理论分析的协同结合，研究人员揭示了药物在缺陷处的对接构象。

据介绍，对于MOF药物输送系统的设计和应用，理解药物-载体的相互作用至关重要。尽管对于有或无缺陷的MOF，这种药物-载体相互作用可能有根本的不同。

附：英文原文

Title: Defect‐assisted Loading and Docking Conformations of Pharmaceuticals in Metal‐Organic Frameworks

Author: Yao Fu, Zhengzhong Kang, Weicheng Cao, Jinglin Yin, Yaoquan Tu, Jianhua Li, Hanxi Guan, Yiran Wang, Qi Wang, Xueqian Kong

Issue&Volume: 05 January 2021

Abstract: The understanding of drug‐carrier interactions is essential for the design and applications of metal‐organic framework (MOF)‐based drug delivery systems. While such drug‐carrier interactions can be fundamentally different for MOFs with or without defects. In this work, we revealed that the defects in MOFs play a key role in the loading of many pharmaceuticals with phosphate or phosphonate groups. The host‐guest interaction is dominated by the Coulombic attraction between phosphate/phosphonate groups and defect sites and it strongly enhances the loading capacity. For similar molecules without a phosphate/phosphonate group or for MOF without defects, the loading capacity is greatly reduced. We employed solid‐state nuclear magnetic resonance (NMR) and molecular simulations to elucidate the drug‐carrier interaction mechanisms. Through a synergistic combination of experimental and theoretical analyses, the docking conformations of pharmaceuticals at the defects have been revealed.

DOI: 10.1002/anie.202010231

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202010231