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| Author(s): |
Amauri Alves de Souza Júnior
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Araraquara. 2018-11-12. |
| Institution: | Universidade Estadual Paulista (Unesp). Instituto de Química. Araraquara |
| Defense date: | 2018-10-29 |
| Advisor: | Maysa Furlan |
| Abstract | |
The research for new drug candidates by pharmaceutical companies and the development in Brazil of new products applied to human and animal health are processes that require continuous optimization. The metabolomics have contributed effectively to plan efficient strategies applied to the bioprospecting of natural products. In this context, 2H-chromenes and chromanes that show accumulation in Piper aduncum and Peperomia obtusifolia (Piperaceae) were selected for the development of a theoretical/experimental approach applied to the study of complex matrices. For this purpose, quantum-chemical calculations based on density functional theory were applied to predict some thermochemical parameters of benzopyrans, including proton affinity, gas-phase basicity and reaction coordinate energy diagrams. Such computational parameters were employed in synergy with the ESI(+)-MS/MS data, aiming to describe the fragmentation profile of the 2H-chromene and chromane, including the description of classical fragmentation mechanisms and specific dissociations for each subclass. Among these aspects, the prenylated 2H-chromene showed that the addition of the proton at the double bond of the prenyl unit is related to a 6-member transition state. Besides that, the thermochemical parameters have shown that the nucleophilicity of the pyran ring of the chromans depends on the C2-linked substituents. Thus, increased contribution by hyperconjugation favored the heterolytic cleavage of the O-C2 bond of the pyran ring. Consequently, a bifurcation in the fragmentation of the chromane derivatives justified adequately the formation of the diagnostic ion after the loss of 122 u. In most works, this fragmentation is explained by the concerted mechanism of retro Diels Alder. In this perspective, the fragmentation pattern of 2H-chromenes and chromanes corroborated with the ion distribution in the energy-resolved plot, and with the energy profile measured in the B3LYP/6-31+G(d,p) model. Using the fragmentation reactions studied by ESI(+)-MS/MS, structural analysis and identification for 2H-chromenes and chromanes were described from the analysis of mass spectra acquired in the mixture. Therefore, the present work confirmed that the integrated use of analytical and computational tools are efficient approaches for identification of natural compounds in complex matrices. (AU) | |
| FAPESP's process: | 14/22239-8 - Metabolomic studies of Piperaceae species by MS and NMR: development of analytical methods and dereplication strategies for exploitation of substances of therapeutic interest |
| Grantee: | Amauri Alves de Souza Júnior |
| Support Opportunities: | Scholarships in Brazil - Doctorate |