Laskin Julia, Futrell Jean H
Pacific Northwest National Laboratory, Fundamental Science Directorate, P.O. Box 999 (K8-88), Richland, Washington 99352, USA.
Mass Spectrom Rev. 2003 May-Jun;22(3):158-81. doi: 10.1002/mas.10041.
In the last decade, the characterization of complex molecules, particularly biomolecules, became a focus of fundamental and applied research in mass spectrometry. Most of these studies utilize tandem mass spectrometry (MS/MS) to obtain structural information for complex molecules. Tandem mass spectrometry (MS/MS) typically involves the mass selection of a primary ion, its activation by collision or photon excitation, unimolecular decay into fragment ions characteristic of the ion structure and its internal excitation, and mass analysis of the fragment ions. Although the fundamental principles of tandem mass spectrometry of relatively small molecules are fairly well-understood, our understanding of the activation and fragmentation of large molecules is much more primitive. For small ions, a single energetic collision is sufficient to dissociate the ion; however, this is not the case for complex molecules. For large ions, two fundamental limits severely constrain fragmentation in tandem mass spectrometry. First, the center-of-mass collision energy-the absolute upper limit of energy transfer in a collision process-decreases with increasing mass of the projectile ion for fixed ion kinetic energy and neutral mass. Secondly, the dramatic increase in density of states with increasing internal degrees of freedom of the ion decreases the rate of dissociation by many orders of magnitude at a given internal energy. Consequently, most practical MS/MS experiments with complex ions involve multiple-collision activation (MCA-CID), multi-photon activation, or surface-induced dissociation (SID). This review is focused on what has been learned in recent research studies concerned with fundamental aspects of MCA-CID and SID of model peptides, with an emphasis on experiments carried out with Fourier transform ion cyclotron resonance mass spectrometers (FT-ICR MS). These studies provide the first quantitative comparison of gas-phase multiple-collision activation and SID of peptide ions. Combining collisional energy-resolved data with RRKM-based modeling revealed the effect of peptide size and identity on energy transfer in collisions-very important characteristics of ion activation from fundamental and the analytical perspectives. Finally, the combination of FT-ICR with SID was utilized to carry out the first time-resolved experiments that examine the kinetics of peptide fragmentation. This has lead to the discovery that the time-dependence of ion dissociation varies smoothly up to a certain collision energy, and then shifts dramatically to a time-independent, extensive dissociation. This near-instantaneous "shattering" of the ion generates a large number of relatively small fragment ions. Shattering of ions on surfaces opens up a variety of dissociation pathways that are not accessible with multiple-collision and multiphoton excitation.
在过去十年中，复杂分子尤其是生物分子的表征成为质谱基础研究和应用研究的重点。这些研究大多利用串联质谱（MS/MS）来获取复杂分子的结构信息。串联质谱（MS/MS）通常包括对母离子进行质量选择，通过碰撞或光子激发使其活化，单分子衰变成具有离子结构特征及其内部激发的碎片离子，以及对碎片离子进行质量分析。尽管相对小分子的串联质谱基本原理已得到较好理解，但我们对大分子的活化和碎片化的认识仍较为原始。对于小离子，单次高能碰撞就足以使离子解离；然而，对于复杂分子并非如此。对于大离子，两个基本限制严重制约了串联质谱中的碎片化。首先，对于固定的离子动能和中性质量，质心碰撞能量（碰撞过程中能量转移的绝对上限）会随着入射离子质量的增加而降低。其次，随着离子内部自由度增加，态密度急剧增加，在给定内能下，解离速率降低了多个数量级。因此，大多数针对复杂离子的实际MS/MS实验涉及多次碰撞活化（MCA-CID）、多光子活化或表面诱导解离（SID）。本综述聚焦于近期有关模型肽MCA-CID和SID基础方面的研究成果，重点是使用傅里叶变换离子回旋共振质谱仪（FT-ICR MS）进行的实验。这些研究首次对肽离子的气相多次碰撞活化和SID进行了定量比较。将碰撞能量分辨数据与基于RRKM的模型相结合，揭示了肽的大小和特性对碰撞中能量转移的影响——从基础和分析角度来看，这都是离子活化非常重要的特征。最后，FT-ICR与SID相结合，首次进行了研究肽碎片化动力学的时间分辨实验。这导致发现离子解离的时间依赖性在达到一定碰撞能量之前会平滑变化，然后急剧转变为与时间无关的广泛解离。离子在表面的这种近乎瞬间的“破碎”会产生大量相对较小的碎片离子。离子在表面的破碎开辟了多种多碰撞和多光子激发无法实现的解离途径。
