Understanding the fragmentation mechanisms of methoxy-, mesyl-, and tosyl-lapachol derivatives by computational chemistry and mass spectrometry analysis

Author(s)

Vessecchi, Ricardo ; Borges, Leticia da Silva ; Emery, Flavio da Silva ; Lopes, Norberto Peporine

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MASS SPECTROMETRY; v. 418, p. 9-pg., 2017-07-01.

Abstract

Quinone derivatives are promising anticancer, antimalarial, and antileishmanial drug candidates. Lapachol is the main natural quinonoid compound studied to date. The synthesis of lapachol (2-hydroxy3-(3-methyl-2-butenyl)-1,4-naphthoquinone) derivatives can help characterization of these compounds in biological matrixes or extracts, particularly by electrospray ionization tandem mass spectrometry (ESI-MS/MS). The synthesized 2-methoxy-, 2-tosyl- and 2-mesyl- derivatives were protonated and fragmented by collisional-induced dissociation (CID); their fragmentation mechanisms were proposed based on CID results and DFT calculations. Quantum Theory of Atoms-in-Molecules, QTAIM, was performed and the bond weakening/reinforcement from bond critical point analysis of electronic densities was used to suggest the fragmentation pathways. Results herein were compared to data previously reported for lapachol (2-hydroxy-1,4-naphthoquinone). The tosyl derivative underwent an interesting fragmentation mechanism, which was comparable to the mechanism undergone by protonated lapachol. Therefore, identifying these compounds by the product-ions produced during ESI-MS/MS spectrometry is feasible. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 14/23604-1 - Computational chemistry: a tool to studies of mass spectrometry, reactivity and fragmentation/reaction mechanisms of organic compounds
• Grantee: Ricardo Vessecchi Lourenço
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50265-3 - Distribution and metabolism of natural and synthetic xenobiotics: from the comprehension of reactional process to tissue imaging generation
• Grantee: Norberto Peporine Lopes
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants