Showing papers by "Rosa M. Claramunt published in 2018"

A vibrational circular dichroism (VCD) methodology for the measurement of enantiomeric excess in chiral compounds in the solid phase and for the complementary use of NMR and VCD techniques in solution: the camphor case

Abstract: For the first time, the success of a methodology for the determination of enantiomeric excess (% ee) in chiral solid samples by vibrational circular dichroism (VCD) spectroscopy is reported. We have used camphor to determine the % ee in a blind sample constituted by a mixture of its two enantiomers as a test for the validity of our approach. IR and VCD spectra of different enantiomeric mixtures of R/S-camphor in Nujol mulls were recorded and linear regressions of VCD intensities (ΔAbs.) vs. % ee for selected bands were found. Finally, the VCD intensities of a blind sample were interpolated in these linear regressions, obtaining its % ee with a rms of 2.4. These results in the solid phase were complemented with the determination of % ee in the liquid phase by VCD and NMR techniques, which are proved to be complementary techniques to carry out this kind of analysis. In the same way as in the VCD solid phase, linear regressions of ΔAbs. vs. % ee for selected bands were established, obtaining a rms of 1.1 in the % ee determination of a blind sample. 1H NMR experiments at 600 MHz using the chiral solvating agent, (S,S)-ABTE, allow the determination of the proportions of enantiomers in CD2Cl2 solution with great accuracy. 13C CPMAS NMR spectra prove that this technique cannot be used for conglomerates and/or solid solutions.

Evaluation of the Antioxidant and Neuroprotectant Activities of New Asymmetrical 1,3-Diketones.

Abstract: A series of fourteen new asymmetrical 1,3-diketone derivatives have been synthesized and evaluated in the ABTS, FRAP and DPPH assays as a new chemotype with antioxidant and drug-like properties. All the compounds displayed low cytotoxicity in comparison to curcumin against the human neuroblastoma SH-SY5Y cell line. Among them, (3Z,5E)-6-(2,5-difluoro-4-hydroxy-phenyl)-1,1,1-trifluoro-4-hydroxyhexa-3,5-dien-2-one (6b) and (3Z,5E)-6-(2,3-difluoro-4-hydroxy-phenyl)-1,1,1-trifluoro-4-hydroxyhexa-3,5-dien-2-one (7b) with excellent solubility and chemical stability in biorelevant media, have also shown a similar Fe+2 chelation behavior to that of curcumin. Additionally, both derivatives 6b and 7b have afforded good neuroprotection activity against H2O2 induced oxidative stress in the same neuronal cell line, with a significant reduction of intracellular ROS levels, in parallel with a good recovery of the Mitochondrial Membrane Potential (ΔΨm). Compounds 6b and 7b with a promising antioxidant and drug-like profile, with low cytotoxic and good neuroprotectant activity, constitute a new interesting chemical class with high potential as new therapeutic agents against neurodegenerative diseases.

The structures of 1,4‐diaryl‐5‐trifluoromethyl‐1H‐1,2,3‐triazoles related to J147, a drug for treating Alzheimer's disease

Abstract: J147 [N-(2,4-dimethylphenyl)-2,2,2-trifluoro-N′-(3-methoxybenzylidene)acetohydrazide] has recently been reported as a promising new drug for the treatment of Alzheimer's disease. The X-ray structures of seven new 1,4-diaryl-5-tri­fluoro­methyl-1H-1,2,3-triazoles, namely 1-(3,4-di­methyl­phen­yl)-4-phenyl-5-tri­fluoro­methyl-1H-1,2,3-triazole (C17H14F3N3, 1), 1-(3,4-di­methyl­phen­yl)-4-(3-meth­oxy­phen­yl)-5-tri­fluoro­methyl-1H-1,2,3-triazole (C18H16F3N3O, 2), 1-(3,4-di­methyl­phen­yl)-4-(4-meth­oxy­phen­yl)-5-tri­fluoro­methyl-1H-1,2,3-triazole (C18H16F3N3O, 3), 1-(2,4-di­­methyl­phen­yl)-4-(4-meth­oxy­phen­yl)-5-tri­fluoro­methyl-1H-1,2,3-triazole (C18H16F3N3O, 4), 1-[2,4-bis­(tri­fluoro­meth­yl)phen­yl]-4-(3-methoxy­phen­yl)-5-tri­fluoro­methyl-1H-1,2,3-triazole (C18H10F9N3O, 5), 1-(3,4-di­meth­oxy­phen­yl)-4-(3,4-di­meth­oxy­phen­yl)-5-tri­fluoro­methyl-1H-1,2,3-triazole (C19H18F3N3O4, 6) and 3-[4-(3,4-di­meth­oxy­phen­yl)-5-(tri­fluoro­meth­yl)-1H-1,2,3-triazol-1-yl]phenol (C17H14F3N3O3, 7), have been determined and compared to that of J147. B3LYP/6-311++G(d,p) calculations have been performed to determine the potential surface and mol­ecular electrostatic potential (MEP) of J147, and to examine the correlation between hydrazone J147 and the 1,2,3-triazoles, both bearing a CF3 substituent. Using MEPs, it was found that the minimum-energy conformation of 4, which is nearly identical to its X-ray structure, is closely related to one of the J147 seven minima.

Libration of phenyl groups detected by VT-SSNMR: Comparison with X-ray crystallography.

Abstract: The X-ray crystal structure of 2-benzyl-1H-benzimidazole, 2BnBzIm, was determined at 293 K showing no dynamic phenomena (disorder) of any class. On the other hand, some 13 C NMR signals were absent in the CPMAS spectrum (100 MHz, 300 K). We decided to carry out variable-temperature SSNMR and discovered that the missing signals are ortho and meta carbons of the phenyl ring of the benzyl group. Line-shape analysis and the Eyring equation were used to determine the barrier, which was compared with the calculated DFT for the gas phase that it is much lower.