Central Analytical Research Facility, Institute for Future Environments , Queensland University of Technology , Brisbane , Queensland 4001 , Australia.
Mass Spectrometry User Resource and Research Facility , University of Wollongong , Wollongong , New South Wales 2522 , Australia.
Anal Chem. 2018 Apr 17;90(8):5343-5351. doi: 10.1021/acs.analchem.8b00469. Epub 2018 Apr 6.
Separation and structural identification of lipids remain a major challenge for contemporary lipidomics. Regioisomeric lipids differing only in position(s) of unsaturation are often not differentiated by conventional liquid chromatography-mass spectrometry approaches leading to the incomplete, or sometimes incorrect, assignation of molecular structure. Here we describe an investigation of the gas phase separations by differential-mobility spectrometry (DMS) of a series of synthetic analogues of the recently described 1-deoxysphingosine. The dependence of the DMS behavior on the position of the carbon-carbon double bond within the ionized lipid is systematically explored and compared to trends from complementary investigations, including collision cross-sections measured by drift tube ion mobility, reaction efficiency with ozone, and molecular dynamics simulations. Consistent trends across these modes of interrogation point to the importance of direct, through-space interactions between the charge site and the carbon-carbon double bond. Differences in the geometry and energetics of this intramolecular interaction underpin DMS separations and influence reactivity trends between regioisomers. Importantly, the disruption and reformation of these intramolecular solvation interactions during DMS are proposed to be the causative factor in the observed separations of ionized lipids which are shown to have otherwise identical collision cross-sections. These findings provide key insights into the strengths and limitations of current ion-mobility technologies for lipid isomer separations and can thus guide a more systematic approach to improved analytical separations in lipidomics.
脂质的分离和结构鉴定仍然是当代脂质组学的主要挑战。仅在不饱和位置（s）上有所不同的位置异构体通常不能通过常规的液相色谱-质谱方法来区分，导致分子结构的不完全或有时不正确的分配。在这里，我们描述了对最近描述的 1-脱氧鞘氨醇的一系列合成类似物的气相通过差分迁移谱（DMS）分离的研究。系统地研究了离子化脂质内碳-碳双键位置对 DMS 行为的影响，并与互补研究中的趋势进行了比较，包括通过漂移管离子迁移测量的碰撞截面、与臭氧的反应效率以及分子动力学模拟。这些询问模式的一致趋势表明，电荷位点与碳-碳双键之间的直接、空间相互作用非常重要。这种分子内相互作用的几何形状和能量学差异是 DMS 分离的基础，并影响区域异构体之间的反应性趋势。重要的是，在 DMS 过程中这些分子内溶剂化相互作用的破坏和重新形成被认为是观察到的离子化脂质分离的原因，这些脂质的碰撞截面实际上是相同的。这些发现为当前用于脂质异构体分离的离子迁移技术的优缺点提供了重要的见解，并因此可以指导更系统的方法来改善脂质组学中的分析分离。
