Alinezhad Vida, Ng Yuen Ki, Mehta Sanvid, Konermann Lars
Department of Chemistry, The University of Western Ontario, London, Ontario N6A 5B7, Canada.
J Am Chem Soc. 2024 Oct 2;146(39):26726-26742. doi: 10.1021/jacs.4c05760. Epub 2024 Sep 17.
Electrospray ionization (ESI) of serine (Ser) solution generates SerH as an abundant magic number cluster. ESI clustering of most other solutes yields nonspecific stoichiometries. It is unclear why SerH dominates in the case of Ser, and how SerH forms during ESI. Even the location of SerH formation is contentious (in solution, in ESI droplets, or elsewhere). Here we unravel key aspects of the l-SerH formation pathway. Harsh ion sampling conditions promote the collision-induced dissociation (CID) of regular ESI analytes. Unexpectedly, SerH was seemingly resistant against CID during ion sampling, despite its extremely low tandem mass spectrometry (MS/MS) stability. This unusual behavior reveals that SerH forms during ion sampling. We propose the following pathway: (1) Nonspecific Ser clusters are released when ESI droplets evaporate to dryness. These initial clusters cover a wide size range, from a few Ser to hundreds or thousands of monomers. (2) The clusters undergo dissociation during ion sampling, mostly via successive loss of neutral monomers. For any source activation voltage, there is a subpopulation of clusters for which this CID cascade tends to terminate at the octamer level, culminating in SerH-dominated product distributions. Mobile proton molecular dynamics simulations were used to model the entire pathway. SerH structures formed in these simulations were consistent with ion mobility experiments. The most compact structures resembled the model of [Scutelnic, V. 2018, 140, 7554-7560], with numerous intermolecular salt bridges and H-bonds. Our findings illustrate how the interplay of association and dissociation reactions across phase boundaries can culminate in magic number clusters.
丝氨酸（Ser）溶液的电喷雾电离（ESI）会产生SerH作为一种丰富的幻数簇。大多数其他溶质的ESI聚类会产生非特异性化学计量。目前尚不清楚为什么在Ser的情况下SerH占主导地位，以及SerH在ESI过程中是如何形成的。甚至SerH形成的位置也存在争议（在溶液中、在ESI液滴中或其他地方）。在这里，我们揭示了l-SerH形成途径的关键方面。苛刻的离子采样条件会促进常规ESI分析物的碰撞诱导解离（CID）。出乎意料的是，尽管SerH的串联质谱（MS/MS）稳定性极低，但在离子采样过程中它似乎对CID具有抗性。这种不寻常的行为表明SerH是在离子采样过程中形成的。我们提出以下途径：（1）当ESI液滴蒸发至干燥时，会释放出非特异性的Ser簇。这些初始簇的尺寸范围很广，从几个Ser到数百或数千个单体。（2）这些簇在离子采样过程中发生解离，主要是通过连续失去中性单体。对于任何源激活电压，都有一部分簇的CID级联倾向于在八聚体水平终止，最终导致以SerH为主的产物分布。使用移动质子分子动力学模拟对整个途径进行建模。在这些模拟中形成的SerH结构与离子迁移实验一致。最紧凑的结构类似于[Scutelnic, V. 2018, 140, 7554 - 7560]的模型，具有大量分子间盐桥和氢键。我们的研究结果说明了跨相边界的缔合和解离反应的相互作用如何最终形成幻数簇。
