Shepard Hawkins S, Zlibut Emanuel, May Jody C, Blakley Benjamin K, McLean John A
Department of Chemistry, Center for Innovative Technology, Vanderbilt University, Nashville, TN 37235, USA.
Phys Chem Chem Phys. 2025 Aug 26. doi: 10.1039/d5cp01748c.
Cyclodextrins (CDs) are macrocyclic oligosaccharides that have the ability to form host-guest inclusion complexes due to their amphiphilic properties, thereby allowing for an increase in the solubility and bioavailability of encapsulated small molecules, such as food constituents and active pharmaceutical ingredients (APIs). While solution-phase properties of CD inclusion complexes have been extensively studied, less is known about the prevailing coordination environment of metal-CD complexes in the absence of bulk solvent. Here, we investigate the gas-phase structural implications of alkali-metal complexation with the three naturally occurring cyclodextrins (αCD, βCD, and γCD) and a suite of linear maltodextrins using structurally-selective ion mobility-mass spectrometry (IM-MS) analysis. For the maltodextrins, the IM-MS analysis revealed an expected linear relationship between the number of monosaccharide units and the measured collision cross section (CCS), however, the CDs exhibited complex size-mass behavior, notably with βCD adopting nearly the same CCS values as the larger γCD, irrespective of the charge carrier. CCS measurements in helium drift gas were obtained on a drift tube IM instrument and used to align to computational modeling outputs which were interpreted for atomistic-level information including bond distances and coordination geometries. Predicted structures for [CD + Na] indicate the unusual gas-phase structural behavior of CDs is a consequence of different charge location preferences for αCD and γCD βCD. Taken together, this work provides a structural context for the underlying metal-host interactions that serve as scaffolds for higher-order CD complexation and supramolecular assemblies.
环糊精（CDs）是大环寡糖，由于其两亲性，能够形成主客体包合物，从而提高被包封的小分子（如食品成分和活性药物成分（API））的溶解度和生物利用度。虽然CD包合物的溶液相性质已得到广泛研究，但对于在没有大量溶剂的情况下金属-CD配合物的主要配位环境了解较少。在这里，我们使用结构选择性离子淌度-质谱（IM-MS）分析，研究碱金属与三种天然存在的环糊精（αCD、βCD和γCD）以及一系列线性麦芽糊精络合的气相结构影响。对于麦芽糊精，IM-MS分析揭示了单糖单元数量与测量的碰撞截面（CCS）之间预期的线性关系，然而，CDs表现出复杂的尺寸-质量行为，特别是βCD与较大的γCD采用几乎相同的CCS值，与电荷载体无关。在漂移管IM仪器上获得了氦漂移气体中的CCS测量值，并用于与计算建模输出对齐，这些输出被解释为包括键距和配位几何结构在内的原子水平信息。[CD + Na]的预测结构表明，CDs异常的气相结构行为是αCD和γCD βCD电荷位置偏好不同的结果。综上所述，这项工作为潜在的金属-主体相互作用提供了结构背景，这些相互作用作为高阶CD络合和超分子组装的支架。
