Ion mobility mass spectrometry with molecular modelling to reveal bioactive isomer conformations and underlying relationship with isomerization
Ion mobility mass spectrometry with molecular modelling to reveal bioactive isomer conformations and underlying relationship with isomerization
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离子淌度质谱与分子建模揭示生物活性异构体构象以及与异构化的潜在关系
DOI：
10.1002/rcm.8271
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发表时间：
2018
影响因子：
2
通讯作者：
Feng Yulin
中科院分区：
文献类型：
--
作者：
Ouyang Hui;Bo Tao;Zhang Zhengxiang;Guo Xinqiu;He Mingzhen;Li Junmao;Yang Shilin;Ma Xin;Feng Yulin
在医学和药物开发中，分子建模是一个重要的工具。开发一个连接理论结构模型和实验测量结果的平台是很有吸引力的。此外，生物活性成分异构体的分离和结构分析仍然是具有挑战性的任务。方法漂移管离子迁移率(IM)质谱仪(MS)提供了包含结构信息的实验碰撞截面(CCS)。实验CCS可以与分子模型结构的计算CCS相比较。这项技术对草药中的生物活性成分特别有用，因为具有相同化学式的活性异构体在这些样品中很常见。结果选择了咖啡酰奎宁酸(CQA)和二咖啡酰奎宁酸(di-CQA)两种模型生物活性成分，系统考察了溶液、离子源条件和离子加热对CCS异构体分布的影响。通过比较计算的CCS和实验值，我们确定了CQA的有利构象。CQA最紧凑的构象比更长的构象更不容易异构化。结果表明，异构化趋势与构象优势度相一致。结论本研究为预测和揭示中草药有效成分的构象和异构化提供了一种有效的方法。
RationaleIn medicine and drug development, molecular modelling is an important tool. It is attractive to develop a platform connecting the theoretical structural modelling and the results from experimental measurement. In addition, the separation and structural analysis of bioactive constituent isomers are still challenging tasks.MethodsDrift tube ion mobility (IM) mass spectrometry (MS) provides the experimental collision cross section (CCS) which contains the structural information. The experimental CCS can be compared with the calculated CCS of the molecular modelling structures. This technique is especially useful for bioactive constituents in herbal medicine because active isomers with the same chemical formula are common in these samples. IM helps separate and identify these isomers and reveals details about their structures and conformations.ResultsTwo model bioactive constituents, caffeoylquinic acids (CQAs) and dicaffeoylquinic acids (di‐CQAs), were selected to systematically investigate the influence of solution, ion source conditions and ion heating on the isomer CCS distributions. By comparing the calculated CCS with the experimental value, we identified the favorable conformations of CQAs. The most compact conformation of a CQA was less likely to isomerize than the more extended conformation. It was found that the isomerization tendency was in accord with the conformation favorability.ConclusionsThis study offers an effective approach to predict and demystify the conformation and isomerization of the active constituents in herbal medicines.