Ion mobility-mass spectrometry is a useful tool in separation of biological isomers, including clinically relevant analytes such as 25-hydroxyvitamin D3 (25OHD3) and its epimer, 3-epi-25-hydroxyvitamin D3 (epi25OHD3). Previous research indicates that these epimers adopt different gas-phase sodiated monomer structures, either the "open" or "closed" conformer, which allow 25OHD3 to be readily resolved in mixtures. In the current work, alternative metal cation adducts are investigated for their relative effects on the ratio of "open" and "closed conformers. Alkali and alkaline earth metal adducts caused changes in the 25OHD3 conformer ratio, where the proportion of the "open" conformer generally increases with the size of the metal cation in a given group. As such, the ratio of the "open" conformer, which is unique to 25OHD3 and absent for its epimer, can be increased from approximately 1:1 for the sodiated monomer to greater than 8:1 for the barium adduct. Molecular modeling and energy calculations agree with the experimental results, indicating that the Gibbs free energy of conversion from the "closed" to the "open" conformation decreased with increasing cation size, correlating with the variation in ratio between the conformers. This work demonstrates the effect of cation adducts on gas-phase conformations of small, flexible molecules and offers an additional strategy for resolution of clinically relevant epimers.

中文翻译：

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通过离子迁移率质谱法和理论建模测量的 25-羟基维生素 D3-阳离子加合物中的依赖于阳离子的构象

离子淌度质谱法是分离生物异构体的有用工具，包括临床相关分析物，如 25-羟基维生素 D3 (25OHD3) 及其差向异构体 3-epi-25-羟基维生素 D3 (epi25OHD3)。先前的研究表明，这些差向异构体采用不同的气相钠化单体结构，无论是“开放”还是“封闭”构象异构体，这使得 25OHD3 很容易在混合物中分离。在目前的工作中，研究了替代金属阳离子加合物对“开放”和“封闭构象异构体”比例的相对影响。碱金属和碱土金属加合物引起了 25OHD3 构象异构体比例的变化，其中“开放”构象异构体的比例通常随着给定组中金属阳离子的大小而增加。因此，“开放”的比率 构象异构体是 25OHD3 独有的并且其差向异构体不存在，可以从钠化单体的大约 1:1 增加到钡加合物的大于 8:1。分子建模和能量计算与实验结果一致，表明从“封闭”构象转换为“开放”构象的吉布斯自由能随着阳离子尺寸的增加而降低，这与构象异构体之间比率的变化相关。这项工作证明了阳离子加合物对小而灵活的分子的气相构象的影响，并提供了一种解决临床相关差向异构体的额外策略。分子建模和能量计算与实验结果一致，表明从“闭合”到“开放”构象的吉布斯自由能随着阳离子尺寸的增加而降低，这与构象异构体之间比率的变化相关。这项工作证明了阳离子加合物对小而灵活的分子的气相构象的影响，并提供了一种解决临床相关差向异构体的额外策略。分子建模和能量计算与实验结果一致，表明从“闭合”到“开放”构象的吉布斯自由能随着阳离子尺寸的增加而降低，这与构象异构体之间比率的变化相关。这项工作证明了阳离子加合物对小而灵活的分子的气相构象的影响，并提供了一种解决临床相关差向异构体的额外策略。