离子移动性质谱法策略,以阐明非共价宿主/宿主复合物的无水结构
Jody C May1, Emanuel Zlibut1, Benjamin K Blakley1
1Department of Chemistry, Center for Innovative Technology, Vanderbilt University, Nashville, Tennessee 37235, United States.
Analytical chemistry
|July 16, 2024
概括
结构质谱 (MS) 技术揭示了14种药物化合物中的11种如何与β-cyclodextrin (βCD) 形成纳入复合体. 这项研究为使用多个MS方法解释客/主复杂结构提供了路线图.
科学领域:
- 分析化学 分析化学
- 结构生物学 结构生物学
- 制药科学 制药科学
背景情况:
- 结构质谱 (MS) 对于分析非共价客/宿主复杂化至关重要.
- 对于解释药物宿主复合体的MS数据,特别是关于纳米封装的MS数据,存在有限的指导.
- 了解这些相互作用对于开发新的药物输送系统至关重要.
研究的目的:
- 描述药物和类似药物的分子形成与β-cyclodextrin (βCD) 复合物的倾向.
- 建立一个综合战略,使用多种MS技术和计算建模来阐明客/主复合体的结构.
- 在宿主-客人化学的背景下,为解释MS数据提供一个框架.
主要方法:
- 使用能量解析MS (ERMS) 和离子移动MS (IM-MS) 进行结构特征.
- 采用以实验MS数据为指导的计算建模,用于结构预测.
- 分析了IM-MS的碰撞横截面 (CCS) 数据,以评估气相复杂结构.
主要成果:
- 在14种药物/类似药物的化合物中,11种药物/类似药物的化合物与βCD.形成了1:1的客/宿主复合体.
- 离子移动性CCS分析表明客/宿主复合体的气相压缩.
- ERMS 分离通道为计算建模提供了电荷站点分配的信息,从而导致优先考虑的结构候选.
结论:
- 结合MS和计算方法成功阐明了客/主复合体的结构.
- 大多数特征无水复合体被确定为含有βCD的包容复合体.
- 这项工作为利用结构MS技术在没有水的情况下研究宿主-客的复杂结构提供了有价值的路线图.
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