Abstract
| I. | Introduction | 159 |
| II. | Experimental Techniques | 160 |
| | A. Gas‐Phase Multiple‐Collision Activation (MCA‐CID) | 160 |
| | 1. On‐Resonance Excitation | 160 |
| | 2. Off‐Resonance Excitation | 161 |
| | 3. Distribution of the Number of Collisions | 161 |
| | 4. Pressure Profile | 162 |
| | B. Surface‐Induced Dissociation (SID) | 162 |
| III. | Collisional Energy Deposition Function (CEDF) | 163 |
| | A. Direct Measurement of the CEDF | 163 |
| | B. Thermometer Ion Method | 164 |
| | C. Recursive Internal Energy Distribution Search Method (RIEDS) | 164 |
| | D. RRKM Modeling of Fragmentation Efficiency Curves | 164 |
| IV. | Factors That Affect the CEDF and the Efficiency of Energy Transfer | 165 |
| | A. Collision Energy and the Pressure of the Collision Gas | 165 |
| | B. Method of Collisional Activation (MCA‐CID or SID) | 166 |
| | C. Properties of the Ion | 167 |
| | 1. MCA‐CID | 167 |
| | 2. SID | 168 |
| V. | Master Equation Modeling | 169 |
| VI. | Fragmentation Efficiency Curves (FECs) | 170 |
| | A. Experimental Parameters | 171 |
| | B. Properties of the Precursor Ion | 172 |
| | C. Slow vs. Fast Ion Activation | 174 |
| VII. | Shattering of Peptide Ions on Surfaces | 175 |
| | A. FT‐ICR SID Experiments | 175 |
| | B. Theoretical Description of Shattering | 176 |
| VIII. | Concluding Remarks | 178 |
| Acknowledgments | | 178 |
| References | | 178 |
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. © 2003 Wiley Periodicals, Inc., Mass Spec Rev 22:158–181, 2003; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/mas.10041