Regioselectivity in the Nitration of Eugenol Is Independent of Inorganic Reagents: An Experimental and Theoretical Investigation with Synthetic and Mechanistic Implications.

In this study, we reinvestigated the straightforward nitration of eugenol using traditional reagents and bismuth nitrate. NMR analysis of the obtained products revealed that the regioselectivity of eugenol nitration was independent of the inorganic nitrating reagent used, consistently resulting in the formation of 6-nitroeugenol. This contradicts previous literature reports because the elusive synthesis of 5-nitroeugenol using Bi(NO3)3·5H2O was not achievable through straightforward methods; instead, this isomer could only be prepared via the well-established three-step synthesis. Theoretical investigations using DFT calculations, considering both the dielectric constant of the medium and explicit water molecules, substantiated this regioselectivity. It was found that hydration water played a critical role in the formation of a Zundel cation, shifting the thermodynamic equilibrium toward the exclusive production of 6-nitroeugenol. These results imply that all biological studies involving eugenol derivatives synthesized via direct nitration with Bi(NO3)3·5H2O should be reviewed, as they dealt with 6-substituted eugenol derivatives rather than the previously assumed 5-substituted eugenol.

Does Trema micranthum (L.) Blume Produce Cannabinoids?

There are inconclusive claims in the scientific literature that the species Trema micranthum, widely distributed throughout the Brazilian territory, may produce phytocannabinoids, potentially serving as an alternative to Cannabis sativa. In this study, we conducted a comprehensive investigation to assess the presence of phytocannabinoids in two Trema micranthum samples collected in the Midwest region of Brazil. In trying to detect cannabinoids in T. micranthum, a recommended cannabis screening test was employed, the Fast Blue BB Salt (FBBBS) colorimetric assay, followed by thin-layer chromatography (TLC) and instrumental techniques: high-performance liquid chromatography coupled to diode array detector (HPLC-DAD) and gas chromatography coupled to mass spectrometry (GC-MS). When employed without chloroform extraction, the FBBBS reagent yielded positive results for extracts from all parts of T. micranthum (leaves, branches, fruits, and inflorescences). However, these initial positive results from the FBBBS test, suggesting the presence of cannabinoids, were not corroborated by FBBBS followed by chloroform extraction, TLC, or the instrumental techniques used in this study. These additional outcomes suggest that the positive FBBBS test results were likely due to the presence of other phenolic compounds rather than phytocannabinoids. For example, the presence of vitexin-like compounds in T. micranthum extracts might explain the positive FBBBS test results. Therefore, new assertions that T. micranthum produces cannabinoids will require the support of more selective experiments to avoid false-positive claims based on less selective screening tests.

A novel arylpiperazine derivative (LQFM181) protects against neurotoxicity induced by 3- nitropropionic acid in in vitro and in vivo models.

In the pursuit of novel antioxidant therapies for the prevention and treatment of neurodegenerative diseases, three new arylpiperazine derivatives (LQFM181, LQFM276, and LQFM277) were synthesized through a molecular hybridization approach involving piribedil and butylated hydroxytoluene lead compounds. To evaluate the antioxidant and neuroprotective activities of the arylpiperazine derivatives, we employed an integrated approach using both in vitro (SH-SY5Y cells) and in vivo (neurotoxicity induced by 3-nitropropionic acid in Swiss mice) models. In the in vitro tests, LQFM181 showed the most promising antioxidant activity at the neuronal membrane and cytoplasmic levels, and significant neuroprotective activity against the neurotoxicity induced by 3-nitropropionic acid. Hence, this compound was further subjected to in vivo evaluation, which demonstrated remarkable antioxidant capacity such as reduction of MDA and carbonyl protein levels, increased activities of succinate dehydrogenase, catalase, and superoxide dismutase. Interestingly, using the same in vivo model, LQFM181 also reduced locomotor behavior and memory dysfunction through its ability to decrease cholinesterase activity. Consequently, LQFM181 emerges as a promising candidate for further investigation into its neuroprotective potential, positioning it as a new therapeutic agent for neuroprotection.