Fragmentation pathway

The following general rules apply to the fragmentation behavior of oligosaccharides 

The major fragmentation pathways relevant to carbohydrate MS are summarized 

Description glycosidic cleavage to form an oxonium ion charge retained on nonreducing end positive-ion mode only often referred to as A -type cleavage, because of similarity to one of the cleavages seen in electron impact-mass spectrometry. 

Description glycosidic cleavage with a hydrogen transfer charge retained on reducing end positive- and negative-ion modes often referred to as )S-cleavage. 

Description ring cleavage charge retained on nonreducing end infrequent pathway in the positive-ion mode, but a major pathway in the negative mode, because a stable, enolate anion results from loss of the enolic hydrogen atom ions are 42 mass units higher than those formed in Pathway C. 

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Mass Spectrometry Aldehydes and ketones typically give a prominent molecular ion peak m their mass spectra Aldehydes also exhibit an M— 1 peak A major fragmentation pathway for both aldehydes and ketones leads to formation of acyl cations (acylium ions) by cleavage of an alkyl group from the carbonyl The most intense peak m the mass spectrum of diethyl ketone for example is m z 57 corresponding to loss of ethyl radi cal from the molecular ion... 

The mass spectrum of 2-pyrone shows an abundant molecular ion and a very prominent ion due to loss of CO and formation of the furan radical cation. Loss of CO from 4-pyrone, on the other hand, is almost negligible, and the retro-Diels-Alder fragmentation pathway dominates. In alkyl-substituted 2-pyrones loss of CO is followed by loss of a hydrogen atom from the alkyl substituent and ring expansion of the resultant cation to the very stable pyrylium cation. Similar trends are observed with the benzo analogues of the pyrones, although in some cases both modes of fragmentation are observed. Thus, coumarins. 

The chemical potentials and free energies of the 2-isoxazolines have also been studied and the electron impact and chemical ionization mass spectra determined (77MI41614). Fragmentation pathways and retrocycloadditions of various derivatives were discussed in these reports. 

Diphenylthiirene 1-oxide and several thiirene 1,1-dioxides show very weak molecular ions by electron impact mass spectrometry, but the molecular ions are much more abundant in chemical ionization mass spectrometry (75JHC21). The major fragmentation pathway is loss of sulfur monoxide or sulfur dioxide to give the alkynic ion. High resolution mass measurements identified minor fragment ions from 2,3-diphenylthiirene 1-oxide at mje 105 and 121 as PhCO" and PhCS, which are probably derived via rearrangement of the thiirene sulfoxide to monothiobenzil (Scheme 2). 

Nitrogen-containing fulvalenes have not been systematically studied by mass spectroscopy. Only isolated data for several examples of compounds have been reported. Most of the data consist of electron impact (El) mass spectra recorded for analytical purposes. Only a minor fraction dealt with the characterization of ion structures or focused on the effects of substituents, the ring size of fulvalenes, or the number and arrangement of nitrogen atoms and the fragmentation pathways. 

Tlie mass spectra of the parent 3-nitro-l,X-naphthyridines (X = 5,6,7, and 8) and their amino and chloro derivatives feature as main fragmentation pathway the loss of a molecule of NO2 from the molecular ions and further consecutive expulsion of two molecules of HCN. A second fragmentation pathway, although of much smaller intensity, is the loss of NO from the molecular ions, followed by consecutive expulsion of CO and HCN (82MI1 89MI1). 

McLafferty rearrangement (Section 12.3) A mass-spectral fragmentation pathway for carbonyl compounds. 

Even though a good fit is not obtained, the library search may indicate the structural type. Review the characteristic fragment pathways of the suspected structural type in Part II of this book, and check Part III to determine if the ions observed and neutral losses correspond to the suggested structural type. 

The other fragmentation pathways are typical for diaryl sulfoxides1-4-6,1. A corresponding ortho effect was found in chlorodiphenyl ethers and sulfides but not in sulfones12 (12) were the sulfinate ester rearrangements1-4,6,11 and the consequent formation of the m/z 125 and m/z 159 ions suppress the other possible fragmentations of the molecular ions (equation 4). It is also noteworthy that the ratio [m/z 125] [m/z 159] increases with increasing distance between the chlorine and the sulfur (equation 4). 

Phenanthro[4,5-b, c, d]thiophene 4-oxide (19) and 4,4-dioxide (20)15 undergo first the well-known sulfenate (22) or sulfinate ester (23) rearrangements1 4,6, respectively (equation 6). The sulfoxide loses an oxygen atom and enters the fragmentation pathway of 18 or loses HCO (more likely in two steps) from 22. Both sulfenate and sulfinate ions can fragment further via 21 after losing a sulfur atom or eliminating SO5, respectively. 

Figure 5.47 Fragmentations pathways for (a) non-demethylated, and (b) demethylated metabolites of Bosentan. Reprinted by permission of Elsevier Science from Exact mass measurement of product ions for the structural elucidation of drug metabolites with a tandem quadrupole orthogonal-acceleration time-of-flight mass spectrometer , by Hopf-gartner, G., Chernushevich, I. V., Covey, T., Plomley, J. B. and Bonner, R., Journal of the American Society for Mass Spectrometry, Vol. 10, pp. 1305-1314, Copyright 1999 by the American Society for Mass Spectrometry.

The examples chosen above have illustrated how CVF or MS-MS may be used to generate useful structural information but these do not always provide sufficient detail to allow an unequivocal structural assigmnent. There may still be instances where it might be necessary to probe fragmentation pathways further. This can be accomplished by combining MS-MS with CVF, i.e. use CVF to effect fragmentation of an ion of interest and then study one of the product ions so formed by using conventional MS-MS. This may be considered to be MS-MS-MS . 

Figure 5.63 Proposed fragmentation pathway of the molecular ion from 8-hydroxy-2 -deoxyguanosine generated by negative ionization. Reprinted by permission of Elsevier Science from Comparison of negative- and positive-ion electrospray tandem mass spectrometry for the liquid chromatography-tandem mass spectrometry analysis of oxidized deoxynucleosides , by Hua, Y., Wainhaus, S. B., Yang, Y., Shen, L., Xiong, Y., Xu, X., Zhang, F., Bolton, J. L. and van Breemen, R. B., Journal of the American Society for Mass Spectrometry, Vol. 12, pp. 80-87, Copyright 2000 by the American Society for Mass Spectrometry.

Ion trap MS is particularly suited for chemical structure elucidation, as it allows for simultaneous ion storage, ion activation and fragmentation, and product ion analysis. The fragmentation pathway of selected ions and the fragmentation products provide information on the molecular structure. Compared with triple-quadrupole and especially with sector instruments, the ion trap instrument provides more efficient conversion of precursor ion into product ions. However, the CID process via resonance excitation, although quite efficient in terms of conversion yield, generally results in only one (major) product ion in the product-ion mass spectrum. MS/MS with a quadrupole ion trap offers a number of advantages ... 

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