Ion mobility mass spectrometry with molecular modelling to reveal bioactive isomer conformations and underlying...

In 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.

Drift 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.

Two 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.

This study offers an effective approach to predict and demystify the conformation and isomerization of the active constituents in herbal medicines.