Proton-bound complex mediating retro-Michael-type fragmentation of protonated 3-substituted oxindoles in the Orbitrap high-energy collisional dissociation cell.

RATIONALE

Oxindole derivatives are valuable building blocks for indole chemistry. Systematically exploring the fragmentation behavior of the protonated 3-pyrazole-substituted oxindoles by kinetic methods combined with density functional theory (DFT) calculations is useful for further understanding their basic properties, and might provide some insights into their reactivity trends in synthesis and metabolism.

METHODS

All high-resolution high-energy collision-induced dissociation tandem mass spectrometry (CID-MS/MS) experiments were carried out using electrospray ionization hybrid Quadrupole-Orbitrap mass spectrometry in positive ion mode. Theoretical calculations were carried out by the DFT method at the B3LYP level with the 6-311G (d, p) basis set in the Gaussian 03 package of programs.

RESULTS

In the fragmentation of protonated 3-pyrazole-substituted oxindoles, the characterized protonated 3-(3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene)indolin-2-one derivatives and the protonated 5-methylpyrazolone were observed, which were proposed from the cleavage of the C(β)-C(γ) bond in a retro-Michael reaction. With the kinetic plot, a linear correlation was established between the intensities of this two competitive product ions and the difference in proton affinities of the corresponding neutral molecules, which demonstrated that the retro-Michael reaction was mediated by a proton-bound complex.

CONCLUSIONS

Using the kinetic method combined with theoretical calculations, a proton-bound complex mediating retro-Michael reaction was proposed for the fragmentation of protonated 3-pyrazole-substituted oxindoles in the high-energy collisional dissociation tandem mass spectrometry for the first time, which provided potential evidence to further understand their intrinsic bioactivities.