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Isocyanates are highly relevant industrial intermediates for polyurethane production. In this work, we used quantum chemistry and transition state theory (TST) to investigate the gas-phase reaction of isocyanates with the OH radical, which is likely one of the most significant chemical sinks for these compounds in the troposphere.

A major part of chemical conversions is carried out in the fluid phase, where an accurate modeling of the involved reactions requires to also take into account solvation effects. Implicit solvation models often cover these effects with sufficient accuracy but can fail drastically when specific solvent–solute interactions are important. In those cases, microsolvation, i.e., the explicit inclusion of one or more solvent molecules, is a commonly used strategy. Nevertheless, microsolvation also introduces new challenges—a consistent workflow as well as strategies how to systematically improve prediction performance are not evident. For the COSMO and COSMO-RS solvation models, this work proposes a simple protocol to decide if microsolvation is needed and how the corresponding molecular model has to look like. To demonstrate the improved accuracy of the approach, specific application examples are presented and discussed, i.e., the computation of aqueous pKa values and a mechanistic study of the methanol mediated Morita–Baylis–Hillman reaction.

The acetate-initiated aliphatic isocyanate trimerization to isocyanurate was investigated by state-of-the-art analytical and computational methods. Although the common cyclotrimerization mechanism assumes the consecutive addition of three equivalents of isocyanate to acetate prior to product formation, we found that the underlying mechanism is more complex. In this work, we demonstrate that the product, in fact, is formed via the connection of two unexpected catalytic cycles, with acetate being only the precatalyst. The initial discovery of a precatalyst activation by quantum chemical computations and the resulting first catalysis cycle were corroborated by mass spectrometric and NMR experiments, thereby additionally revealing a catalyst migration to the second catalytic cycle. These results were further confirmed by computations, completing the full mechanistic understanding of this catalytic system. Identification of a side product with undesired properties for final coating applications allows for process optimization in the chemical industry.

Die einfache Erzeugung von Titanocen(III)-Hydriden ermoglicht Epoxid-Hydrosilylierungen mit geringen Katalysatormengen, hohen Ausbeuten und Selektivitaten in der Radikalreduktion. Die Untersuchung des Mechanismus mittels kinetischer, EPR-spektroskopischer und theoretischer Methoden legt einen ungewohnlichen Ruhezustand des Katalysators nahe, der zu einer inversen Reaktionsordnung im Epoxid fuhrt.

The host-guest complexation of hydrocarbons (22 guest molecules) with cucurbit[7]uril (CB7) was investigated in aqueous solution. Association constants were determined by using the indicator displacement strategy, which allows binding constant determinations also for poorly water-soluble (hydrophobic) guests. The binding constants (103–109 M−1) increased with the size of the hydrocarbon, pointing to the hydrophobic effect and dispersion interactions as driving forces. Besides potential applications for the sensing and separation of hydrocarbons, the measured affinities provide unique benchmark data for the binding of neutral guest molecules. Consequently, a computational blind challenge, the HYDROPHOBE challenge, was conducted in order to allow a comparison with state-of-the-art computational methods for predicting host-guest affinity constants. In total, 5 computational data sets were submitted, which allowed the comparison of experimental binding constants with those predicted by coupled-cluster theory (DLPNO-CCSD(T)), dispersion-corrected density functional theory (DFT), and explicit solvent molecular dynamics (MD) simulations parameterized with two different force field combinations from the AMBER simulation package. All submissions were capable of predicting the general binding trend, with a slightly better correlation for the MD compared to the quantum-chemical (QM) data sets (R2MD = 0.80 vs R2QM = 0.66, average values for the submitted data sets). On the other hand, QM calculations showed better predictions for the absolute values of the binding affinities as reflected by the mean signed errors (4.3 kcal mol−1 for MD vs 1.8 kcal mol−1 for QM). When searching for sources of uncertainty in predicting the host-guest affinities, the experimentally known hydration energies of the investigated hydrocarbons could be employed, which provided a distinct advantage of the HYDROPHOBE challenge. The comparison with the employed solvation models (explicit solvent for MD and COSMO-RS for QM) confirmed a good correlation for both methods, but revealed a rather constant offset of the COSMO data, by ca. +2 kcal mol−1, which was traced back to a required reference-state correction in the QM submissions (2.38 kcal mol−1). Introduction of the reference-state correction improved the predictive power of the QM methods, particularly for small hydrocarbons up to C5. The correlations of both QM and MD submissions also exposed specific outliers, which could be due to peculiarities of the investigated guests, for example, different degrees of conformational changes upon complexation, such as helical structures of the longer n-alkyl chains within the cavity. The latter was confirmed by 2D NMR experiments and both the MD as well as QM calculations.

Despite the fact that functionalized planar chiral [2.2]paracyclophanes have received a lot of attention, the chemistry of pseudo-meta 4,15-distubstituted [2.2]paracyclophanes is largely unexplored. This is mainly due to the fact that the 4,5-dibromo-functionalized [2.2]paracyclophane is much less prone to halogen-metal exchange reactions than its constitutional pseudo-ortho or pseudo-para isomers. Here, we give an account of an efficient protocol to achieve this, which allows the synthesis of a broad variety of 4,15-disubstituted [2.2]paracyclophanes. Furthermore, we were able to resolve several of the racemic compounds via chiral HPLC and assign the absolute configurations of the isolated enantiomers by X-ray diffraction and/or by the comparison of calculated and measured CD-spectra.

Association free energies ΔGa are calculated for two different types of host-guest systems, the rigid cucurbit[7]uril (CB7) and the basket shaped octa-acid (OA), and a number of charged guest molecules each by quantum chemical methods from first principles in the context of a recent blind test challenge (SAMPL4). For CB7, the overall agreement between theory and experiment is excellent. In comparison with all other submitted calculated relative ΔGa,rel values for this part of the blind test, our results ranked on top. Modeling the binding free energy in the case of the OA host mainly suffers from the problem that the binding situation is undefined with respect to the charge state and due to its intrinsic flexibility the host-guest complex is not represented well by a single configuration, but qualitative features of the binding process such as the proper binding orientation and the order of magnitude of ΔGa are represented in accord with the experimental expectations even though an accurate ranking is not possible.

A catalytic system for titanocene-catalyzed epoxide hydrosilylation is described. It features a straightforward preparation of titanocene hydrides that leads to a reaction with low catalyst loading, high yields, and high selectivity of radical reduction. The mechanism was studied by a suite of methods, including kinetic studies, EPR spectroscopy, and computational methods. An unusual resting state leads to the observation of an inverse rate order with respect to the epoxide.

The S12L test set for supramolecular Gibbs free energies of association ΔGa (Grimme, S. Chem. Eur. J. 2012, 18, 9955-9964) is extended to 30 complexes (S30L), featuring more diverse interaction motifs, anions, and higher charges (-1 up to +4) as well as larger systems with up to 200 atoms. Various typical noncovalent interactions like hydrogen and halogen bonding, π-π stacking, nonpolar dispersion, and CH-π and cation-dipolar interactions are represented by "real" complexes. The experimental Gibbs free energies of association (ΔGa exp) cover a wide range from -0.7 to -24.7 kcal mol-1. In order to obtain a theoretical best estimate for ΔGa, we test various dispersion corrected density functionals in combination with quadruple-ζ basis sets for calculating the association energies in the gas phase. Further, modern semiempirical methods are employed to obtain the thermostatistical corrections from energy to Gibbs free energy, and the COSMO-RS model with several parametrizations as well as the SMD model are used to include solvation contributions. We investigate the effect of including counterions for the charged systems (S30L-CI), which is found to overall improve the results. Our best method combination consists of PW6B95-D3 (for neutral and charged systems) or ωB97X-D3 (for systems with counterions) energies, HF-3c thermostatistical corrections, and Gibbs free energies of solvation obtained with the COSMO-RS 2012 parameters for nonpolar solvents and 2013-fine for water. This combination gives a mean absolute deviation for ΔGa of only 2.4 kcal mol-1 (S30L) and 2.1 kcal mol-1 (S30L-CI), with a mean deviation of almost zero compared to experiment. Regarding the relative Gibbs free energies of association for the 13 pairs of complexes which share the same host, the correct trend in binding affinities could be reproduced except for two cases. The MAD compared to experiment amounts to 1.2 kcal mol-1, and the MD is almost zero. The best-estimate theoretical corrections are used to back-correct the experimental ΔGa values in order to get an empirical estimate for the "experimental", zero-point vibrational energy exclusive, gas phase binding energies. These are then utilized to benchmark the performance of various "lowcost" quantum chemical methods for noncovalent interactions in large systems. The performance of other common DFT methods as well as the use of semiempirical methods for structure optimizations is discussed.

In quantum chemical computations the combination of Hartree–Fock or a density functional theory (DFT) approximation with relatively small atomic orbital basis sets of double‐zeta quality is still widely used, for example, in the popular B3LYP/6‐31G* approach. In this Review, we critically analyze the two main sources of error in such computations, that is, the basis set superposition error on the one hand and the missing London dispersion interactions on the other. We review various strategies to correct those errors and present exemplary calculations on mainly noncovalently bound systems of widely varying size. Energies and geometries of small dimers, large supramolecular complexes, and molecular crystals are covered. We conclude that it is not justified to rely on fortunate error compensation, as the main inconsistencies can be cured by modern correction schemes which clearly outperform the plain mean‐field methods.