Effects of Alkali Metal Ion Cationization on Fragmentation Pathways of Triazole-Epothilone

Abstract

The collisionally activated dissociation mass spectra of the protonated and alkali metal cationized ions of a triazole-epothilone analogue were studied in a Fourier transform ion cyclotron resonance mass spectrometer. The fragmentation pathway of the protonated ion was characterized by the loss of the unit of C 3 H 4 O 3 . However, another fragmentation pathway with the loss of C 3 H 2 O 2 was identified for the complex ions with Na + , K + , Rb + , and Cs + . The branching ratio of the second pathway increases with the increment of the size of alkali metal ions. Theoretical calculations based on density functional theory (DFT) method show the difference in the binding position of the proton and the metal ions. With the increase of the radii of the metal ions, progressive changes in the macrocycle of the compound are induced, which cause the corresponding change in their fragmentation pathways. It has also been found that the interaction energy between the compound and the metal ion decreases with increase in the size of the latter. This is consistent with the experimental results, which show that cesiated complexes readily eject Cs + when subject to collisions.

Intramolecular oxo‐Diels–Alder rearrangement in collisionally activated dissociation of protonated ions of a mactrocyclic molecule: triazole‐epothilone dimer

“…Among them, the latter four fragment ions are consistent with those observed in the CAD mass spectrum of the protonated ions of triazole-epothilone monomer 4 (m/z 505.25). [11] Previous studies of the protonated ions of 4 suggest that in their dissociation process, the bonds broken first are 1a and 1b (Scheme 1 and Scheme S1 in supporting information). Then, the formed fragment ions (m/z 417.23) can be further dissociated by breaking the bonds 1c, 1d and 1e in turn, forming fragment ions at 317.…”

“…This pathway is characterized by breaking the bonds 1a′ and 1b (Scheme 1). [11] It is also found that the branching ratio of this pathway increases with the increase of the size of the combined alkali metal ion. In order to better understand the effects of alkali metal ion on fragmentation pathways of compound 5 and, particularly, the intramolecular oxo-Diels-Alder reaction, the alkali metal cationized ions of 5 are studied by CAD MS, too.…”

“…Recently, Chen group reported the effective synthesis of a triazole-epothilone analogue (compound 4 in Scheme 1) with Cu 2 O nanoparticle-catalyzed azide-alkyne cycloaddition reaction. [10] The effects of alkali metal ion cationization on the fragmentation pathways of 4 have been studied by tandem MS. [11] With the increase of the radii of the metal ions, progressive structural changes in the macrocycle of 4 are induced, causing their fragmentation pathways to correspondingly change. It is noted that a byproduct of triazole-epothilone dimer (compound 5 in Scheme 1) was also generated by the same reaction.…”

“…Table 1) to those generated by both Path 3 and Path 2 for compound 5 (circles), as a function of effective metal ionic radius. For comparison, the corresponding values for compound 4 (squares) [11] are also shown in the figure. The ionic radii are taken from reference.…”

Structural Characterization of Anticancer Drug Paclitaxel and Its Metabolites Using Ion Mobility Mass Spectrometry and Tandem Mass Spectrometry

“…In addition, diverse interactions between different metal cations and ligand molecules allow unique structural rearrangements and dissociation pathways [31,32]. Recent studies demonstrated the effect of alkali metal and silver metal cations to generate different CID patterns [33][34][35]. In case of alkali metal cations, the ion sizes and binding properties influence the complex structures and CID patterns [33,36].…”