Neutral loss fragmentation reactions

TABLE 7.8 Common Neutral Loss Fragments Observed in Reaction 7.17... 

These rearrangement reactions may also occur in MS-MS instruments and the constant-neutral-loss scan enables the analyst to observe all of the ions in the mass spectrum that fragment with a particular mass loss and therefore contain a specific structural feature. This knowledge can be of great value when attempting to interpret the mass spectrum of an unknown material. 

Processes such as decarbonylation, decarboxylation, elimination of water, and several other reactions may also occur prior to ionization, i.e., as non-mass spectral reactions, typically as a result of thermal degradation upon heating of the sample to enforce evaporation. In such a case, the mass spectrum obtained is not that of the analyte itself, but of its decomposition product(s). Sometimes, those thermal reactions are difficult to recognize, because the same neutral loss may also occur by a true mass spectral fragmentation of the corresponding molecular ion. 

Nitroarenes are recognized from their characteristic neutral losses due to the NO2 substituent. Normally, all theoretically possible fragment ions, the plausible [M-N02] and [M-O] ions as well as the unexpected [M-NO] ion, are observed. It is worth noting that molecular ions are 1,2-distonic by definition, because nitroarene molecules are best represented as zwitterion (Chap. 6.3). The molecular ion may either dissociate directly by loss of an oxygen atom or a NO2 molecule or it may rearrange prior to loss of NO. For the latter process, two reaction pathways have been uncovered, one of them involving intermediate formation of a nitrite, and the other proceeding via a three-membered cyclic intermediate. [208]... 

High-throughput analysis requires speed of analysis, hence no chromatographic separation of analytes and detection by making use of a common fragmentation reaction (neutral loss). 

Selected Reaction Monitoring (MS/MS) Selected reaction monitoring (SRM) is the process by which the first mass analysis selects a specific m/z (the precursor ion) to be fragmented in the collision cell and the second mass analysis selects and detects a specific product ion. Most commonly used in the quantitative analysis of well-characterized, targeted species for which optimized precursor-product pairs can be established. In SRM-based LC-MS assays no qualitative information can be obtained. However, SRM can be used to trigger product ion, neutral loss, or precursor ion scans. 

There are two general types of fragmentation reactions. In one type the radical cation fragments to a neutral molecule and a new radical cation. This process is especially favorable when the neutral product is a small, stable molecule. For example, the loss of water from the molecular ion of alcohols is very facile. For this reason the M+ peak is very small for primary and secondary alcohols, and it is usually undetectable for... 

DBT, 2-DBT (2-methyldibenzo[3]thiophene), and 4,6-DBT (4,6-dimethyldibenzo[3]thiophene) in ESI tandem mass spectra have a a consistent 32 Da neutral loss, which is believed to be sulfur. Based on the tandem mass spectrum of the PASH compounds, the mechanism of fragmentation is considered to be a charge site-initiated reaction followed by a radical site-initiated fragmentation. Taking the example of DBT, Scheme 4 shows a possible mechanism. 

Figure 7 Scan modes for a tandem-in-space instrument, the triple quadruple (QqQ). (a) Full scan all source ions are passed through to Q3 while Q1 and q (collision cell) are set to the RF-only mode, (b) Production scan Qi is set to pass a selected ion (precursor ion). This is fragmented in the collision cell and products are analyzed by scanning Q3. (c) Precursor scan Q1 scans all the source ions into the collision cell for collision-induced dissociation (CID). Q3 is set to pass a selected product ion. A signal recorded at Q3 is correlated with the corresponding precursor ion passing through Q-i. (d) Neutral loss scan Q-i is set to scan ions into the collision cell for CID. The Q3 scan is offset by a specified mass, equal to the mass of the neutral, relative to Qi. (e) Selected reaction monitoring (SRM) an ion selected in Q1 is fragmented and a specific fragment is then recorded after selection by Q3. SRM is commonly used in quantitative work to improve assay selectivity and sensitivity.

Comparisons between MS/MS of the (M - HJ- and /M + H]+ Ions of Oligpdeoxynudeotides. Under low-energy CID conditions in the ion-trap, similar classes of ions, such as the base loss nonsequence and the wn sequence ions, are observed in the MS/MS spectra of both the [M - H] and [M + H]+ ions [44]. The key physical organic concepts discussed above can readily be used to provide mechanistic rationals for these fragmentation reactions. For the M + H]+ ions the most likely site of protonation is at the nucleobase sites, which have the higher proton affinity. Thus protonation at these sites acts as a trigger for neutral base loss via El or intramolecular E2 mechanisms [44]. The order of nucleobase loss for the [M + H]+ ions is C > G > A > T. In contrast, for the... 

---