Chiral thiophene sulfonamide : a challenge for VOA calculations

Two enantiomers of 2-methyl-<i>N</i>-(1-thien-2-ylethyl)­propane-2-sulfonamide (TSA) were synthesized, and their VCD, ROA, IR, and Raman spectra were registered. The solved (<i>S</i>)-TSA X-ray structure shows a disorder connected to the presence of two TSA conformers differing by a slight rotation of the thiophene ring. Two molecules in the unit cell of the monoclinic <i>P</i>2₁ crystal form a net of NH···OS and C*H···OS hydrogen bonds. Out of a series of computational levels tested to interpret the spectra, the B3LYP functional combined with the def2TZVP basis set satisfactorily reproduces the experimental VCD and ROA spectra. To simulate the VCD spectra of TSA enantiomers in KBr pellets, dimers and tetramers, with two different positions of the thiophene ring, were considered. The VCD spectra measured in CDCl₃ are completely different from those taken in KBr due to the conformational freedom of TSA in chloroform. Seven TSA conformers fall into two groups of opposite configurations at the pyramidal N atom forming the additional stereogenic center. However, the barriers between conformers in each group are lower than the energy of thermal motions at 300 K. Thus, all conformers, but the most stable in each group, are likely to be metastable states. The calculated IR, VCD, Raman, and ROA spectra of the conformers depend not only on the type of stereogenic N atom but also on the thiophene ring rotation. Yet, they are likely to coexist because of low barriers between them. Three approaches were tested to reproduce the chiroptical spectra in solution using PCM and hybrid solvation models. As a consequence, it was found that a model in which all conformers contribute to the spectra with equal population factors seems to best reproduce the experimental data. Such a result suggests that in a dissolved state in 300 K TSA occurs in a very shallow potential well and all of its conformers coexist

New Derivatives of 3,4-Dihydroisoquinoline-3-carboxylic Acid with Free-Radical Scavenging, D-Amino Acid Oxidase, Acetylcholinesterase and Butyrylcholinesterase Inhibitory Activity

A series of 3,4-dihydroisoquinoline-3-carboxylic acid derivatives were synthesised and tested for their free-radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·), 2,2\u27-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS·+), superoxide anion radical (O2·−) and nitric oxide radical (·NO) assays. We also studied D-amino acid oxidase (DAAO), acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity. Almost each of newly synthesised compounds exhibited radical scavenging capabilities. Moreover, several compounds showed moderate inhibitory activities against DAAO, AChE and BuChE. Compounds with significant free-radical scavenging activity may be potential candidates for therapeutics used in oxidative-stress-related diseases

On Raman optical activity sign-switching between the ground and excited states leading to an unusual resonance ROA induced chirality

Raman optical activity (ROA) spectra recorded for a chiral naphthalene diimide derivative (nBu-NDI–BINAM) dissolved in a series of solvents exhibit strong solute to solvent induced chirality with: (1) dominating bands of solvents, (2) nBu-NDI–BINAM resonance ROA (RROA) bands which are barely visible, (3) monosignate RROA Solvent spectra with an unexpected sign concordant with that of the ECD band of the resonant electronic state, (4) bisignate RROA bands for a few solvents, and (5) superposition of non-resonant and resonant ROA bands of the chiral solvents. The unusual ROA enhancement was explained in terms of resonance energy transfer with resonant Raman emission. The surprising RROA sign-switching was found to be due to specific conformational equilibria where one solute conformer dominates in the ground and the other in the first excited singlet state, and, the signs of the related ECD bands of these two conformers are opposit