Department of Chemistry, University of Waterloo, 200 University Avenue West, Waterloo N2L 3G1, Ontario, Canada.
Watermine Innovation, Waterloo N0B 2T0, Ontario, Canada.
J Am Soc Mass Spectrom. 2021 Apr 7;32(4):956-968. doi: 10.1021/jasms.0c00469. Epub 2021 Mar 18.
The presence of solvent vapor in a differential mobility spectrometry (DMS) cell creates a microsolvating environment that can mitigate complications associated with field-induced heating. In the case of peptides, the microsolvation of protonation sites results in a stabilization of charge density through localized solvent clustering, sheltering the ion from collisional activation. Seeding the DMS carrier gas (N) with a solvent vapor prevented nearly all field-induced fragmentation of the protonated peptides GGG, AAA, and the Lys-rich Polybia-MP1 (IDWKKLLDAAKQIL-NH). Modeling the microsolvation propensity of protonated -propylamine [PrNH], a mimic of the Lys side chain and N-terminus, with common gas-phase modifiers (HO, MeOH, EtOH, PrOH, acetone, and MeCN) confirms that all solvent molecules form stable clusters at the site of protonation. Moreover, modeling populations of microsolvated clusters indicates that species containing protonated amine moieties exist as microsolvated species with one to six solvent ligands at all effective ion temperatures () accessible during a DMS experiment (ca. 375-600 K). Calculated of protonated GGG, AAA, and Polybia-MPI using a modified two-temperature theory approach were up to 86 K cooler in DMS environments seeded with solvent vapor compared to pure N environments. Stabilizing effects were largely driven by an increase in the ion's apparent collision cross section and by evaporative cooling processes induced by the dynamic evaporation/condensation cycles incurred in the presence of an oscillating electric separation field. When the microsolvating partner was a protic solvent, abstraction of a proton from [MP1 + 3H] to yield [MP1 + 2H] was observed. This result was attributed to the proclivity of protic solvents to form hydrogen-bond networks with enhanced gas-phase basicity. Collectively, microsolvation provides analytes with a solvent "air bag," whereby charge reduction and microsolvation-induced stabilization were shown to shelter peptides from the fragmentation induced by field heating and may play a role in preserving native-like ion configurations.
在差分迁移谱（DMS）池中存在溶剂蒸气会产生微溶剂化环境，可减轻与场致加热相关的复杂性。对于肽，质子化部位的微溶剂化会通过局部溶剂聚集稳定电荷密度，从而使离子免受碰撞激活。用溶剂蒸气对 DMS 载气（N）进行种子处理可防止质子化的 GGG、AAA 和富含赖氨酸的 Polybia-MP1（IDWKKLLDAAKQIL-NH）肽几乎所有的场致碎裂。质子化的 -丙胺[PrNH]（赖氨酸侧链和 N 末端的模拟物）与常见气相修饰剂（HO、MeOH、EtOH、PrOH、丙酮和 MeCN）的微溶剂化倾向建模表明，所有溶剂分子都在质子化部位形成稳定的簇。此外，微溶剂化簇的物种模型表明，在 DMS 实验期间（约 375-600 K）可获得有效离子温度（）下，所有含有质子化胺部分的物质都以含有一至六个溶剂配体的微溶剂化物质存在。使用改进的双温理论方法计算的质子化 GGG、AAA 和 Polybia-MPI 的 比在 DMS 环境中用溶剂蒸气种子处理时要低 86 K，而在纯 N 环境中则要低 86 K。稳定化效应主要归因于离子表观碰撞截面的增加以及在存在振荡电场分离的情况下由动态蒸发/冷凝循环引起的蒸发冷却过程。当微溶剂化伴侣是质子溶剂时，从[MP1 + 3H]中提取质子以生成[MP1 + 2H]。这一结果归因于质子溶剂形成具有增强气相碱性的氢键网络的倾向。总的来说，微溶剂化为分析物提供了一个溶剂“气囊”，电荷减少和微溶剂化诱导的稳定化使肽免受场加热引起的碎裂，并可能在保持类似天然的离子构型方面发挥作用。
