We previously discovered that electron attachment to gaseous peptide anions can occur within a relatively narrow electron energy range. The resulting charge-increased radical ions undergo dissociation analogous to conventional cation electron capture/transfer dissociation (ECD/ETD), thus enabling a novel tandem mass spectrometry (MS/MS) technique that we termed negative ion electron capture dissociation (niECD). We proposed that gaseous zwitterionic structures are required for niECD with electron capture either occurring at or being directed by a positively charged site. Here, we further evaluate this zwitterion mechanism by performing niECD of peptides derivatized to alter their ability to form zwitterionic gaseous structures. Introduction of a fixed positive charge tag, a highly basic guanidino group, or a highly acidic sulfonate group to promote zwitterionic structures in singly charged anions, rescued the niECD ability of a peptide refractory to niECD in its unmodified form. We also performed a systematic study of five sets of synthetic peptides with decreasing zwitterion propensity and found that niECD efficiency decreased accordingly, further supporting the zwitterion mechanism. However, traveling-wave ion mobility-mass spectrometry experiments, performed to gain further insight into the gas-phase structures of peptides showing high niECD efficiency, exhibited an inverse correlation between the orientationally averaged collision cross sections and niECD efficiency. These results indicate that compact salt-bridged structures are also a requirement for effective niECD.

中文翻译：

---

盐桥肽阴离子气态结构可实现有效的负离子电子捕获解离

我们之前发现电子与气态肽阴离子的附着可以在相对较窄的电子能量范围内发生。由此产生的电荷增加的自由基离子会发生类似于传统阳离子电子捕获/转移解离 (ECD/ETD) 的解离，从而实现一种新型串联质谱 (MS/MS) 技术，我们将其称为负离子电子捕获解离 (niECD)。我们提出，niECD 需要气态两性离子结构，电子捕获要么发生在带正电的位点上，要么由带正电的位点引导。在这里，我们通过对衍生的肽进行 niECD 来改变其形成两性离子气体结构的能力，进一步评估这种两性离子机制。引入固定正电荷标签、高碱性胍基或高酸性磺酸基以促进单电荷阴离子中的两性离子结构，挽救了未修饰形式的对 niECD 难治的肽的 niECD 能力。我们还对五组两性离子倾向降低的合成肽进行了系统研究，发现 niECD 效率相应降低，进一步支持了两性离子机制。然而，为了进一步了解显示高 niECD 效率的肽的气相结构而进行的行波离子淌度-质谱实验显示，定向平均碰撞截面与 niECD 效率之间呈负相关。这些结果表明紧凑的盐桥结构也是有效 niECD 的要求。