Novel Methods for Chiral Molecules in the Gas Phase and Neoteric Solvents

This thesis focuses on the development and application of computational methods for the calculation of infrared (IR) and vibrational circular dichroism (VCD) spectra in the gas and liquid phase, with special emphasis on (non-idle) solvent effects. The solvents studied in this thesis are mainly alcohols and ionic liquids (ILs), and some of the methods presented are applied to study enantiomeric recognition and chirality transfer mechanisms in the latter. The first part introduces the cluster-weighting (CW) approach for computing bulk phase vibrational spectra. This method is based on a weighted average of quantum-chemically calculated clusters, whose cluster populations are determined by quantum cluster equilibrium (QCE) calculations. Using two uncertainty propagation methods, it is shown that inaccuracies in experimental input data do not significantly affect the outcome of QCE calculations. CW is then used to calculate IR and VCD spectra of neat (R)-butan-2-ol and acetonitrile/(R)-butan-2-ol mixtures, yielding good to excellent agreement with experimental references. It is shown that structures up to hexamers are sufficient to reproduce the main features of the experimental liquid phase spectra, with the best agreement observed for clusters calculated at the BP86/def2-TZVP and B3LYP/def2-TZVP levels of theory. Another method based on ab initio molecular dynamics (AIMD) simulations is shown to yield spectra of higher quality, but at a significantly increased computational cost. Based on this, the computational efficiency of cluster-weighting is emphasized, especially for calculating mole fraction dependent spectral features (e.g., peak shifts) in mixtures. In the second part, enantiomeric recognition and chirality transfer mechanisms in ILs are investigated by AIMD simulations. Dissolution of different D-glucose isomers in dry and moist 1-ethyl-3-methylimidazolium acetate causes chirality transfer from the glucose units to the transiently chiral cation of the IL, resulting in observable VCD activity of the latter. In addition, onsets for crystallization, anomeric conversion, and carbene-like reactions are observed, the understanding of which contributes to the development of new methods for processing glucose and cellulose. The importance of chirality transfer in chiral recognition mechanisms is emphasized by studying the dissolution of (R)- and (S)-butan-2-ol in 1-ethyl-3-methylimidazolium L-alaninate and (R)-1,2-propylene oxide in 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide. While (R)-butan-2-ol and L-alaninate induce the same conformation in the cation, (S)-butan-2-ol induces a mirrored structure, causing an energetic destabilization. (R)-1,2-propylene oxide, on the other hand, is found to selectively transfer chirality to the bis(trifluoromethylsulfonyl)imide anion, leaving the cation unaffected. These findings provide a basis for future research into the targeted application of chirality transfer in enantiomeric recognition processes

Liquid Dynamics Determine Transition Metal-N-Heterocyclic Carbene Complex Formation

The mechanism of metal-N-heterocyclic carbene (NHC) complex formation from imidazolium salts in the presence of weak bases was investigated through theoretical methods. Quantum chemical calculations revealed that the two bases considered here, sodium acetate and trimethylamine, both facilitate complex formation. In contrast to previous experiments, these calculations indicated a slightly lower barrier with the amine. Molecular dynamics simulations showed that the ionic nature of the [AuCl2]− and imidazolium ions, as well as the sodium acetate base keep these species associated in the reaction mixture through ion pairing. This pre-association of the components produces those clusters that are essential for the metal complex formation reaction. The neutral amine, however, remains mostly separated from the other reaction partners, making it a significantly less effective base

Error quantification of phase transition quantities from cluster weighting calculations

The following article has been submitted to The Journal of Chemical Physics. After it is published, it will be found at https://aip.scitation.org/journal/jcp . In this work, we investigate how uncertainties in experimental input data influence the results of quantum cluster equilibrium calculations. In particular, we focus on the calculation of vaporization enthalpies and entropies of seven organic liquids, compare two computational approaches for their calculation and investigate how these properties are affected by changes in the experimental input data. It is observed that the vaporization enthalpies and entropies show a smooth dependence on changes in the reference density and boiling point. The reference density is found to have only a small influence of the vaporization thermodynamics, whereas the boiling point has a large influence on the vaporization enthalpy but only a small influence on the vaporization entropy. Furthermore we employed the Gauss--Hermite estimator in order to quantify the error in the thermodynamic functions that stems from uncertainties in the experimental reference data at the example of the vaporization enthalpy of (R)-butan-2-ol. We quantify the error as 30.95 J/mol. Additionally we compare the convergence behaviour and computational effort of the Gauss--Hermite estimator with the Monte Carlo approach and show the superiority of the former. By this, we present how uncertainty quantification can be applied to examples from theoretical chemistry

Liquid Dynamics Determine Transition Metal-N-Heterocyclic Carbene Complex Formation.

The mechanism of metal-N-heterocyclic carbene (NHC) complex formation from imidazolium salts in the presence of weak bases was investigated through theoretical methods. Quantum chemical calculations revealed that the two bases considered here, sodium acetate and trimethylamine, both facilitate complex formation. In contrast to previous experiments, these calculations indicated a slightly lower barrier with the amine. Molecular dynamics simulations showed that the ionic nature of the [AuCl2 ]- and imidazolium ions, as well as the sodium acetate base keep these species associated in the reaction mixture through ion pairing. This pre-association of the components produces those clusters that are essential for the metal complex formation reaction. The neutral amine, however, remains mostly separated from the other reaction partners, making it a significantly less effective base. © 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH

Liquid dynamics determine transition metal-N-heterocyclic carbene complex formation

Invited for the cover of this issue are Oldamur Hollczki and co-workers at the Universities of Bonn, Ghent and Debrecen. The image depicts the search of an ionic base for the acidic proton of an imidazolium cation in order to form a carbene complex. Read the full text of the article at 10.1002/chem.202203636

Conformer Weighting and Differently Sized Cluster Weighting for Nicotine and Its Phosphorus Derivatives

Weighting methods applied to systems with many conformers have been broadly employed to calculate thermodynamic properties, structural characteristics, and populations. To better understand and test the sensitivity of conventional weighting methods, the conformational distributions of nicotine and its phosphorus-substituted derivatives are investigated. The weighting schemes used for this are all based on Boltzmann statistics. Classical Boltzmann factors based on the electronic energy and the Gibbs free energy are calculated at different quantum chemical levels of theory and compared to cluster weights obtained by the quantum cluster equilibrium method. Furthermore, the influence of the modified rigid-rotor–harmonic-oscillator (mRRHO) approximation on the cluster weights is investigated. The substitution of the nitrogen atom in the methylpyrrolidine ring by a phosphorus atom results in more monomer conformers and clusters being populated. The conformational distribution of the monomers remained stable at different levels of theory and weighting methods. However, going to dimers and trimers, we observe a significant influence of the level of theory, weighting method, and mRRHO cutoff on the populations of these clusters. We show that mRRHO cutoff values of 50 and 100 cm–1 yield similar results, which is why 50 cm–1 is recommended as a robust choice. Furthermore, we observe that the global minimum for ΔE0 and ΔG varies in a few cases and that the global minimum is not always the dominantly occupied structure

Processing Gray Selenium in Phosphonium-Based Ionic Liquids

The dissolution of gray selenium in tetraalkylphosphonium acetate ionic liquids was investigated by UV−vis, NMR, and Raman spectroscopy as well as quantum chemical calculations and electrochemical methods. Acetate anions and tetraalkylphosphonium cations facilitate the formation and stabilization of oligoselenides Sen 2− and cationic Se species in the ionic liquid phase. Chemical exchange of selenium atoms was demonstrated by variable-temperature 77Se NMR experiments. Additionally, uncharged cycloselenium molecules exist at high selenium concentrations. Upon dilution with ethanol, amorphous red selenium precipitates from the solution. Moreover, crystalline Se1−xTex solid solutions precipitate when elemental tellurium is added to the mixture as confirmed by powder X-ray diffraction and Raman spectroscopy

Identification and characterization of the bacterial etiology of clinically problematic acute otitis media after tympanocentesis or spontaneous otorrhea in German children

Abstract Background Acute Otitis Media (AOM) is an important and common disease of childhood. Bacteria isolated from cases of clinically problematic AOM in German children were identified and characterized. Methods In a prospective non-interventional study in German children between 3 months and less than 60 months of age with Ear, Nose and Throat Specialist –confirmed AOM, middle ear fluid was obtained by tympanocentesis (when clinically indicated) or by careful sampling of otorrhea through/at an existing perforation. Results In 100 children with severe AOM, Haemophilus influenzae was identified in 21% (18/21, 85.7% were non-typeable [NTHi]), Streptococcus pneumoniae in 10%, S. pyogenes in 13% and Moraxella catarrhalis in 1%. H. influenzae was the most frequently identified pathogen in children from 12 months of age. H. influenzae and S. pneumoniae were equally prevalent in children aged 3–11 months, but S. pyogenes was most frequently isolated in this age group. NTHi AOM disease appeared prevalent in all ages. Conclusions NTHi, S. pneumoniae and S. pyogenes are implicated as important causes of complicated AOM in children in Germany. NTHi disease appears prevalent in all ages. The impact of vaccination to prevent NTHi and S. pneumoniae AOM may be substantial in this population and is worth investigating.</p