Synthesis and VCD Spectroscopic Characterization of a Series of Azacryptands from a Chiral Valine-Based Derivative of Tris(2-aminoethyl)amine (TREN).

Utilizing experimental and computational vibrational circular dichroism (VCD) spectroscopy, we explored the conformational preferences of a series of chiral C3 -symmetric octaazacryptands with tris(2-aminoethyl)-amine head groups derived from valine. While the spectra of the smallest azacryptand with p-phenyl linkers and its elongated derivative with p-biphenyls linker were found to match well with the computed spectra, the computed conformational preferences of the m-biphenyl-based azacryptand did not seem to reflect the conformations dominating in chloroform solution. A detailed analysis revealed that structural changes resulting in a collapsed cage structure gave a notably better match with the experiment. It could subsequently be concluded from the VCD analysis, that the octaazacryptands prefer a collapsed structure, which is not predicted by density functional theory (DFT) calculations as the global minimum structures. These findings are expected to have consequences also for future studies on inclusion complexes of such azacryptands.

Anion-binding of a chiral tris(2-aminoethyl)amine-based tripodal thiourea: a spectroscopic and computational study.

Thioureas are well-known structural motifs in supramolecular anion recognition. Their conformational preferences are typically characterized by detailed NMR spectroscopy and crystallography, which are often complemented with computational results from geometry optimizations. Herein we investigate a chiral tris(thiourea) based on tris(2-aminoethyl)amine, which acts as an anion receptor for chloride and hydrogen sulfate. We show that a detailed NMR analysis led to a rather ambiguous picture of the conformational preferences of 1 in its complexes. The computational results were found to depend heavily on the selected computational level (functionals with or without dispersion corrections) and relative energies (zero-point corrected vs. Gibbs free energies) used for the calculation of the Boltzmann weights. Only the in-depth analysis of the experimentally observed vibrational circular dichroism (VCD) spectra and comparison with computed spectral signatures allowed us to reveal the actual chiral binding orientation in chloroform solution.

Solvation of the Boc-Val-Phe-nPr peptide characterized by VCD spectroscopy and DFT calculations.

The conformational preferences of peptides are strongly determined by hydrogen bonding interactions. Intermolecular solute-solvent interactions compete with intramolecular interactions, which typically stabilize the secondary structure of the peptide. The analysis of vibrational circular dichroism (VCD) spectra can give insights into solvation-induced changes in the conformational distribution of small peptides. Here we describe the VCD spectroscopic characterization of the model peptide Boc-Val-Phe-nPr in chloroform as representative for a weakly interacting solvent and dimethyl sulfoxide (DMSO-d6) as a strongly hydrogen bonding solvent. We show that the conformational preferences of the peptide in chloroform are well-described by the computationally predicted distribution of the isolated molecule assuming only implicit solvation effects through a continuum solvation model. In order to simulate the spectra recorded in DMSO-d6, solvation was accounted for explicitly by computed microsolvated structures containing one to three solvent molecules. A good match of the computed spectra with the experimental data is obtained by this method. Comparing the conformational distributions in deuterated chloroform-d1 and DMSO-d6, structures with intramolecular hydrogen bonds such as the (δ,δ)-conformer family contribute to the conformational distribution only when there is no strong interaction with the solvent. This is in contrast to the results for the related Boc-Pro-Phe-nPr studied before, for which the intramolecular interaction was found to persist in DMSO-d6. Furthermore, we discuss the influence of hydrogen bonding to different numbers of solvent molecules on the spectral signatures and show that the structure of the peptide in DMSO-d6 is best described as a mixture of twofold-solvated (δ,ß)- and threefold-solvated (ß,ß)-conformers.

Basis set dependence of S[double bond, length as m-dash]O stretching frequencies and its consequences for IR and VCD spectra predictions.

Benchmarking functionals and basis sets for the computational prediction of molecular properties is usually done on very small model systems. Larger organic molecules containing heavier second row atoms are not the typical model structures. We herein present the first survey of basis sets and functionals for the prediction of the IR and VCD spectra of chiral tosylates and sulfinates as we noted drastic deviations between computed harmonic frequencies obtained at B3LYP/6-311++G(2d,p) level of theory and those observed in experimental solution phase IR and VCD spectra. We show that the harmonic frequencies of the asymmetric and symmetric S[double bond, length as m-dash]O stretching modes of tosylates are predicted at significantly too low vibrational frequencies if the employed basis set does not provide higher order polarization functions. The results of our benchmarks show that at least the 6-311G(3df,2dp) basis (or equivalent Dunning and Ahlrichs variants) should be used.

Isolation of the right upper-lobe with a left-sided double-lumen tube after left-pneumonectomy.

A patient with a prior left pneumonectomy required surgical drainage of a right upper lobe aspergilloma. A left double-lumen endobronchial tube was placed in the right bronchus intermedius, isolating the right upper lobe while allowing ventilation of the right middle and lower lobes.