Zheng Xueyun, Renslow Ryan S, Makola Mpho M, Webb Ian K, Deng Liulin, Thomas Dennis G, Govind Niranjan, Ibrahim Yehia M, Kabanda Mwadham M, Dubery Ian A, Heyman Heino M, Smith Richard D, Madala Ntakadzeni E, Baker Erin S
Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory , Richland, Washington 99354, United States.
Department of Biochemistry, University of Johannesburg , P.O. Box 524, Auckland Park 2006, South Africa.
J Phys Chem Lett. 2017 Apr 6;8(7):1381-1388. doi: 10.1021/acs.jpclett.6b03015. Epub 2017 Mar 15.
Due to the recently uncovered health benefits and anti-HIV activities of dicaffeoylquinic acids (diCQAs), understanding their structures and functions is of great interest for drug discovery efforts. DiCQAs are analytically challenging to identify and quantify since they commonly exist as a diverse mixture of positional and geometric (cis/trans) isomers. In this work, we utilized ion mobility spectrometry coupled with mass spectrometry to separate the various isomers before and after UV irradiation. The experimental collision cross sections were then compared with theoretical structures to differentiate and identify the diCQA isomers. Our analyses found that naturally the diCQAs existed predominantly as trans/trans isomers, but after 3 h of UV irradiation, cis/cis, cis/trans, trans/cis, and trans/trans isomers were all present in the mixture. This is the first report of successful differentiation of cis/trans diCQA isomers individually, which shows the great promise of IMS coupled with theoretical calculations for determining the structure and activity relationships of different isomers in drug discovery studies.
由于最近发现二咖啡酰奎宁酸（diCQAs）对健康有益且具有抗HIV活性，了解其结构和功能对于药物研发工作具有重要意义。由于diCQAs通常以位置异构体和几何异构体（顺式/反式）的多种混合物形式存在，因此对其进行分析鉴定和定量具有挑战性。在这项工作中，我们利用离子淌度光谱法结合质谱法，在紫外线照射前后分离各种异构体。然后将实验碰撞截面与理论结构进行比较，以区分和鉴定diCQA异构体。我们的分析发现，天然的diCQAs主要以反式/反式异构体形式存在，但在紫外线照射3小时后，混合物中同时存在顺式/顺式、顺式/反式、反式/顺式和反式/反式异构体。这是首次成功单独区分顺式/反式diCQA异构体的报告，表明离子淌度光谱法结合理论计算在药物研发研究中确定不同异构体的结构与活性关系方面具有巨大潜力。
