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Determination of the absolute configuration of chiral molecules is a prerequisite for obtaining a fundamental understanding in any chirality-related field. The interaction with polarised light has proven to be a powerful means to determine this absolute configuration, but its application rests on the comparison between experimental and computed spectra for which the inherent uncertainty in conformational Boltzmann factors has proven to be extremely hard to tackle. Here we present a novel approach that overcomes this issue by combining a genetic algorithm that identifies the relevant conformers by accounting for the uncertainties in DFT relative energies, and a hierarchical clustering algorithm that analyses the trends in the spectra of the considered conformers and identifies on-the-fly when a given chiroptical technique is not able to make reliable predictions. The effectiveness of this approach is demonstrated by considering the challenging cases of papuamine and haliclonadiamine, two bis-indane natural products with eight chiral centres and considerable conformational heterogeneity that could not be assigned unambiguously with current approaches., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The absolute configuration of a chiral molecule is key to its biological activity. Being able to find out what this configuration is, is thus crucial for a wide range of applications. The difficulties associated with such a determination steeply rise as the number of chiral centers in a given compound becomes larger. Concurrently, it becomes increasingly more challenging to determine the levels and identity of potential stereochemical contaminants in a given sample with one and the same technique, leading in practice to extensive and laborious efforts employing multiple analytical techniques. Here, experimental and theoretical studies based on Vibrational Circular Dichroism (VCD) are presented for dydrogesterone, a synthetic drug employed in reproductive medicine that is a prototypical example of such a multi-center chiral compound. We show that our approach allows us to distinguish and assign its absolute configuration without prior knowledge to one of the 64 possible stereoisomers associated with the six chiral centers. Studies on mixtures of dydrogesterone and 6-dehydroprogesterone, one of the diastereomers of dydrogesterone and generally the dominant impurity of dehydrogesterone, show that we can identify the presence of both compounds from one single VCD spectrum. Moreover, we find that we can determine diastereomeric contamination levels as low as 5% from the experimental VCD spectra., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Upon cooling in solution, chiral triarylamine tris-amide unimers produce organogels by stacking into helical supramolecular polymers, which subsequently bundle into larger fibers. Interestingly, circular dichroism, vibrational circular dichroism, and AFM imaging of the chiral self-assemblies revealed that monocolumnar P-helical fibrils formed upon fast cooling, whereas bundled M-superhelical fibers formed upon slow cooling. The mechanistic study of this structural bifurcation reveals the presence of a strong memory effect, reminiscent of a complex stepwise combination of primary and secondary nucleation-growth processes. These results highlight the instrumental role of sequential self-assembly processes to control supramolecular architectures of multiple hierarchical order., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Vibrational circular dichroism (VCD) studies are reported on a chiral compound in which a fullerene C 60 moiety is used as an electron acceptor and local VCD amplifier for an alanine-based peptide chain. Four redox states are investigated in this study, of which three are reduced species that possess low-lying electronic states as confirmed by UV/Vis spectroelectrochemistry. VCD measurements in combination with (TD)DFT calculations are used to investigate (i) how the low-lying electronic states of the reduced species modulate the amplification of VCD signals, (ii) how this amplification depends on the distance between oscillator and amplifier, and (iii) how the spatial extent of the amplifier influences amplification. These results pave the way for further development of tailored molecular VCD amplifiers., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Collision-induced absorption is the phenomenon in which interactions between colliding molecules lead to absorption of light, even for transitions that are forbidden for the isolated molecules. Collision-induced absorption contributes to the atmospheric heat balance and is important for the electronic excitations of O 2 that are used for remote sensing. Here, we present a theoretical study of five vibronic transitions in O 2 -O 2 and O 2 -N 2 , using analytical models and numerical quantum scattering calculations. We unambiguously identify the underlying absorption mechanism, which is shown to depend explicitly on the collision partner-contrary to textbook knowledge. This explains experimentally observed qualitative differences between O 2 -O 2 and O 2 -N 2 collisions in the overall intensity, line shape and vibrational dependence of the absorption spectrum. It is shown that these results can be used to discriminate between conflicting experimental data and even to identify unphysical results, thus impacting future experimental studies and atmospheric applications.

In the version of this Article originally published, Figures 3 and 4 were erroneously swapped, this has been corrected in all versions of the Article.