TOCSY, hydrogen decoupling and computational calculations to an unequivocal structural elucidation of a new sesquiterpene derivative and identification of other constituents from Praxelis sanctopaulensis.

INTRODUCTION: Praxelis genus comprises 24 species, however, only two species of this genus have been chemically investigated. Here we investigated Praxelis sanctopaulensis, a native plant from Brazil, that occurs mainly in Cerrado regions. OBJECTIVE: The goal was to identify the specialised metabolites from P. sanctopaulensis, and compare with those described from Praxelis and Chromolaena species. METHODS: The phytochemical study of P. sanctopaulensis was performed through different chromatography techniques, including high-performance liquid chromatography (HPLC), gas chromatography flame ionisation detector (GC-FID), and ultra-high-performance liquid chromatography high-resolution tandem mass spectrometry (UHPLC-HRMS/MS). The structures of the compounds were established based on spectroscopic analysis, total correlated spectroscopy (TOCSY), hydrogen decoupling and computational calculations was used to an unequivocal structural elucidation of a new sesquiterpene. The antioxidant activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP), and antimicrobial assay was performed by the microdilution method. Comparison of the flavonoids described P. sanctopaulensis was carried out using principal component analysis. RESULTS: The phytochemical investigation of P. sanctopaulensis led to the isolation of a pair of diastereomers, praxilone A and praxilone B. Seven known compounds were isolated from this species, another 14 fatty acids were detected in hexane fraction, and 26 compounds were identified from ethyl acetate fraction. All these compounds are being described for the first time in this species, with the exception of viridifloric acid. The ethyl acetate fraction showed potent antioxidant activity. CONCLUSIONS: Forty-seven compounds are described from P. sanctopaulensis. The combination of different techniques of nuclear magnetic resonance (NMR) spectroscopy and computational calculations allowed the unequivocal structure elucidation of a new cadinene. The clustering analysis showed similarities between the flavonoids identified in P. sanctopaulensis and in Chromolaena species.

Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines.

The presence of strong stereoelectronic interactions involving the substituents in cis-2-substituted cyclohexanes may lead to results different from those expected. In this work, we studied the conformational behavior of cis-2-fluoro- (F), cis-2-chloro- (Cl), cis-2-bromo- (Br) and cis-2-iodocyclohexylamine (I) by dynamic NMR and theoretical calculations. The experimental data pointed to an equilibrium strongly shifted toward the ea conformer (equatorial amine group and axial halogen), with populations greater than 90% for F, Cl and Br in both dichloromethane-d 2 and methanol-d 4. Theoretical calculations (M06-2X/6-311++G(2df,2p)) were in agreement with the experimental, with no influence of the solvent or the halogen on the equilibrium. A principal component analysis of natural bond orbital energies pointed to the σ*C-X and σC-H orbitals and the halogen lone pairs (LPX) as the most significant for the hyperconjugative interactions that influenced the equilibrium. The σC-H → σ*C-X hyperconjugation and the interactions involving the LPX counterbalance each other, explaining the non-influence of the halogen on the conformational equilibrium. These interactions are responsible for the strong preference for the ea conformer in cis-2-halocyclohexylamines, being strong enough to restrain the shift in the equilibrium due to other factors such as steric repulsion or solvent effects.

Thiosemicarbazone@Gold nanoparticle hybrid as selective SERS substrate for Hg2+ ions.

The Raman spectral profile of p-methylcarbohydrazonethioamide (MCHT) is completely changed due to strong SERS effects upon bonding onto gold nanoparticles surface, but some vibrational modes are further enhanced in the presence of Hg(II) ions. The lack of SERS response for most common metal ions indicates that the coordinating groups are interacting with the gold nanoparticles surface and not available for binding metal ions in solution, except for mercury ions. The selective enhancement of some vibrational modes is consistent with significant conformational changes upon binding of Hg(II) ion onto the AuNP@MCHT hybrid, as confirmed by TEM/EDS measurements, demonstrating its potentiality as a highly selective and sensitive SERS substrate.

Thiosemicarbazone p-Substituted Acetophenone Derivatives Promote the Loss of Mitochondrial Δψ, GSH Depletion, and Death in K562 Cells.

A series of thiosemicarbazone (TSC) p-substituted acetophenone derivatives were synthesized and chemically characterized. The p-substituents appended to the phenyl group of the TSC structures were hydrogen, fluor, chlorine, methyl, and nitro, producing compounds named TSC-H, TSC-F, TSC-Cl, TSC-Me, and TSC-NO2, respectively. The TSC compounds were evaluated for their capacity to induce mitochondrial permeability, to deplete mitochondrial thiol content, and to promote cell death in the K562 cell lineage using flow cytometry and fluorescence microscopy. TSC-H, TSC-F, and TSC-Cl exhibited a bell-shaped dose-response curve for the induction of apoptosis in K562 cells due to the change from apoptosis to necrosis as the principal mechanism of cell death at the highest tested doses. TSC-Me and TSC-NO2 exhibited a typical dose-response profile, with a half maximal effective concentration of approximately 10 µM for cell death. Cell death was also evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which revealed lower toxicity of these compounds for peripheral blood mononuclear cells than for K562 cells. The possible mechanisms leading to cell death are discussed based on the observed effects of the new TSC compounds on the cellular thiol content and on mitochondrial bioenergetics.