Characterization of the fragmentation mechanisms in electrospray ionization tandem mass spectrometry of chloroquinoline derivatives with larvicidal activity against Aedes aegypti

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da Silva, Rodrigo Moreira ; Barbieri, Jessica Guastalli ; Murie, Valter Eduardo ; Silverio, Maira Rosato Silveira ; Soldi, Rafael Augusto ; Albernaz, Lorena Carneiro ; Espindola, Laila Salmen ; Vieira, Paulo Cezar ; Clososki, Giuliano Cesar ; Vessecchi, Ricardo ; Lopes, Norberto Peporine

• Document type: Journal article
• Source: RAPID COMMUNICATIONS IN MASS SPECTROMETRY; v. 38, n. 12, p. 10-pg., 2024-06-30.

Abstract

Rationale: 4,7-Dichloroquinoline (DCQ) represents a group of synthetic molecules inspired by natural products with important roles in biological and biomedical areas. This work aimed to characterize DCQ and its derivatives by high-resolution electrospray ionization (ESI) mass spectrometry and tandem mass spectrometry (ESI-MS/MS), supported by theoretical calculations. Biological assays were carried out with DCQ and its derivatives to determine LC50 values against Aedes aegypti larvae. Methods: Five DCQ derivatives were synthesized by using previously described protocols. ESI-MS/MS analyses were carried out with a quadrupole/time-of-flight and ion-trap instrument. The proposed gas-phase protonation sites and fragmentation were supported by density functional theory calculations. The larvicidal tests were performed with the Ae. aegypti Rockefeller strain, and the LC50 values were determined by employing five test concentrations. Larval mortality was determined after treatment for 48 h. Results: DCQ bromides or aldehydes (C-3 or C-8 positions), as well as the trimethylsilyl derivative (C-3 position), were prepared. Detailed ESI-MS/MS data revealed heteroatom elimination through an exception to the even-electron rule, to originate open-shell species. Computational studies were used to define the protonation sites and fragmentation pathways. High activity of DCQ and its derivatives against Ae. aegypti larvae was demonstrated. Conclusion: Our results provided a well-founded characterization of the fragmentation reactions of DCQ and its derivatives, which can be useful for complementary studies of the development of a larvicidal product against Ae. aegypti. (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: 20/02207-5 - Inventorying secondary metabolism applying metabolomic strategies: contribution to the Brazilian biodiversity valuation
• Grantee: Norberto Peporine Lopes
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants