Phenylisoserine in the gas-phase and water: Ab initio studies on neutral and zwitterion conformers

International audienceThe conformational landscape of phenylisoserine (PhIS) was studied. Trial structures were generated by allowing for all combinations of single-bond rotamers. Based on the B3LYP/aug-cc-pVDZ calculations 54 conformers were found to be stable in the gas phase. The six most stable conformers were further optimized at the B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVDZ levels for which characteristic intramolecular hydrogen bond types were classified. To estimate the influence of water on PhIS conformation, the IEF-PCM/B3LYP/aug-cc-pVDZ calculations were carried out and showed 51 neutral and six zwitterionic conformers to be stable in water solution. According to DFT calculations, the conformer equilibrium in the gas phase is dominated by one conformer, whereas the MP2 calculations suggest three PhIS structures to be significantly populated. Comparison of DFT and MP2 energies of all 57 structures stable in water indicates that, in practice, one zwitterionic and one neutral conformer determine the equilibrium in water. Based on the AIM calculations, we found that for the neutral conformers in vacuum and in water, d(H...B) is linearly correlated with Laplacian at the H-bond critical point

On Stability, Chirality Measures, and Theoretical VCD Spectra of the Chiral C₅₈X₂ Fullerenes (X = N, B)

The stability of all 23 C₅₈N₂ and C₅₈B₂ heterofullerenes in the singlet and triplet states was determined at the B3LYP/6-31G** level. In equilibrium mixture the achiral (1,4) C₅₈N₂ isomer would be populated in ca. 95.8%, the chiral (1,16) one in ca. 3.3%, and the achiral (1,4) C₅₈B₂ in 100%, whereas all triplet state isomers are less stable. Fourteen out of 23 C₅₈X₂ are chiral. Four different chirality measures were calculated by our own CHIMEA program: pure geometrical, labeled, mass, and charge. Intercorrelations between the measures for all chiral compounds indicate that the pure geometrical chirality measure is unstable and should not be used in QSAR predictions of the other molecular properties, while the labeled and mass-weighted ones are promising QSAR descriptors. For each chiral C₅₈N₂ molecule, some very strong VCD bands, of intensity comparable with that in the IR spectra, can serve in identification and characterization of the isomers

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

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

Oxidation of Olefins with Benzeneseleninic Anhydride in the Presence of TMSOTf

A new oxidizing system for olefins, consisting of benzeneseleninic anhydride and trimethylsilyl triflate, was studied. The highly reactive benzeneseleninyl cation is presumably formed under these conditions. It has been shown that different products are formed with this species depending on the specific structure of olefin. The 1,1-disubstituted olefins afforded mostly α,β-unsaturated carbonyl compounds. The sterically encumbered tri- or tetrasubstituted olefins yielded 1,2- or 1,4-dihydroxylated products, presumably via four-membered cyclic intermediates

Exploring the Sponge Consortium <i>Plakortis symbiotica–Xestospongia deweerdtae</i> as a Potential Source of Antimicrobial Compounds and Probing the Pharmacophore for Antituberculosis Activity of Smenothiazole A by Diverted Total Synthesis

Fractionation of the bioactive CHCl₃–MeOH (1:1) extracts obtained from two collections of the sponge consortium <i>Plakortis symbiotica</i>–<i>Xestospongia deweerdtae</i> from Puerto Rico provided two new plakinidone analogues, designated as plakinidone B (<b>2</b>) and plakinidone C (<b>3</b>), as well as the known plakinidone (<b>1</b>), plakortolide F (<b>4</b>), and smenothiazole A (<b>5</b>). The structures of <b>1</b>–<b>5</b> were characterized on the basis of 1D and 2D NMR spectroscopic, IR, UV, and HRMS analysis. The absolute configurations of plakinidones <b>2</b> and <b>3</b> were established through chemical correlation methods, VCD/ECD experiments, and spectroscopic data comparisons. When assayed in vitro against <i>Mycobacterium tuberculosis</i> H₃₇Rv, none of the plakinidones <b>1</b>–<b>3</b> displayed significant activity, whereas smenothiazole A (<b>5</b>) was the most active compound, exhibiting an MIC value of 4.1 μg/mL. Synthesis and subsequent biological screening of <b>8</b>, a dechlorinated version of smenothiazole A, revealed that the chlorine atom in <b>5</b> is indispensable for anti-TB activity