Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, P.O. Box 286, 1519 Budapest, Hungary.
Molecules. 2022 Nov 3;27(21):7514. doi: 10.3390/molecules27217514.
The understanding of the relationship between molecular structure and the thermodynamics of host-guest binding is essential for the rational design of the applications of inclusion complexes. To obtain insight into the factors governing the driving force of complex formation in aqueous solutions, the encapsulation of five pharmaceutically important protoberberine alkaloids was studied in sulfobutylether-β-cyclodextrin having on average 6.4 degrees of substitution (SBE6.4βCD). Spectrophotometric, fluorescence spectroscopic, and isothermal calorimetric measurements showed 1:1 complexation in dilute solutions. From 1.92 × 104 M−1, about an eight-fold decrease of the association constant was observed in the series of berberine ≈ coptisine >> palmatine > epiberberine > dehydrocorydaline. The embedment of these alkaloids in the SBE6.4βCD cavity was entropy-controlled with mildly negative enthalpy contributions. These findings suggest that the stabilization of the examined complexes arises primarily from the hydrophobic interaction between the constituents. The more than three orders of magnitude smaller association constants of protoberberine alkaloids with SBE6.4βCD than with cucurbit[7]uril, a host having similar cavity size, originates from the much smaller exothermicity of the confinement in the former macrocycle.
理解分子结构与主客体结合热力学之间的关系对于包含配合物应用的合理设计至关重要。为了深入了解在水溶液中控制配合物形成驱动力的因素，研究了在平均取代度为 6.4 的磺丁基醚-β-环糊精（SBE6.4βCD）中五种具有药用价值的原小檗碱类生物碱的包合作用。分光光度法、荧光光谱法和等温热力学测量表明在稀溶液中形成 1:1 的配合物。从 1.92×104 M-1 开始，在一系列小檗碱≈黄连碱＞巴马汀＞延胡索乙素＞脱氢紫堇碱中观察到结合常数大约降低了八倍。这些生物碱嵌入 SBE6.4βCD 空腔是熵控制的，伴有略微负的焓贡献。这些发现表明，所研究的配合物的稳定性主要源于组分之间的疏水相互作用。与葫芦[7]脲相比，原小檗碱类生物碱与 SBE6.4βCD 的结合常数大三个数量级以上，这是由于前者大环中束缚的放热量小得多。
