Structural analysis of 2-arylidene-1-indanone derivatives by electrospray ionization tandem mass spectrometry

Authors


  • Dedicated to Dr. Shashikumar K. Paknikar on the occasion of his 78th birthday.

Correspondence to: J. C. J. M. D. S. Menezes and M. R. M. Domingues, QOPNA, Department of Chemistry, University of Aveiro, 3810–193 Aveiro, Portugal.

E-mail: josemenezes@ua.pt; mrd@ua.pt

Abstract

RATIONALE

2-arylidene-4-methoxy (or hydroxy)-7-methyl-1-indanone derivatives inspired from donepezil, the current drug used for the treatment of Alzheimer's disease as inhibitor of acetylcholinesterase (AChE), were studied for the first time by electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS). Structurally, these arylidene-indanone compounds are considered as cyclic analogues of chalcones.

METHODS

ESI-MS and tandem mass spectra were acquired using a Q-TOF 2 instrument. Fragmentation patterns were analyzed by CID-MS2–3 spectra acquired in a Q-TOF and in LXQ linear ion trap mass spectrometers using standard isolation and excitation procedures.

RESULTS

All the 2-arylidene indanones have shown a common fragmentation pathway leading to a (21, 1')A+ product ion at m/z 187 and the retro-aldol product ion [(2, 21)B+] that allow to establish the substitution in the B ring. The effect of electron-donating and -withdrawing substituents on these fragmentation pathways was noticed. The presence of the OCH3, OH, NO2 and Br substituents gave typical fragmentation processes that allowed their unequivocal fingerprinting. The combined loss of the ortho substituent in the B-ring plus hydrogen (H, OCH3, Br and F) is proposed to form a stable cyclic ring product.

CONCLUSIONS

Arylidene indanones with different substituents on the B ring are associated with a specific fragmentation pattern. In addition, differentiation between isomers with substituents in B ring at ortho and para positions were achieved using ESI-MS/MS. These fragmentation pathways can be used to further identify and determine the fate of these molecules in all stages of drug discovery. Copyright © 2013 John Wiley & Sons, Ltd.

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