The application of quantum chemical, automatic multilevel modeling workflows for the determination of thermodynamic (e.g., conformation equilibria, partition coefficients, pK a values) and spectroscopic properties of relatively large, nonrigid molecules in solution is described. Key points are the computation of rather complete structure (conformer) ensembles with extremely fast but still reasonable GFN2-xTB or GFN-FF semiempirical methods in the CREST searching approach and subsequent refinement at a recently developed, accurate r 2 SCAN-3c DFT composite level. Solvation effects are included in all steps by accurate continuum solvation models (ALPB, (D)COSMO-RS). Consistent inclusion of thermostatistical contributions in the framework of the modified rigid-rotor-harmonic-oscillator approximation (mRRHO) based on xTB/FF computed PES is also recommended.

We present a robust and efficient method to implicitly account for solvation effects in modern semiempirical quantum mechanics and force fields. A computationally efficient yet accurate solvation model based on the analytical linearized Poisson–Boltzmann (ALPB) model is parameterized for the extended tight binding (xTB) and density functional tight binding (DFTB) methods as well as for the recently proposed GFN-FF general force field. The proposed methods perform well over a broad range of systems and applications, from conformational energies over transition-metal complexes to large supramolecular association reactions of charged species. For hydration free energies of small molecules, GFN1-xTB­(ALPB) is reaching the accuracy of sophisticated explicitly solvated approaches, with a mean absolute deviation of only 1.4 kcal/mol compared to the experiment. Logarithmic octanol–water partition coefficients (log K ow) are computed with a mean absolute deviation of about 0.65 using GFN2-xTB­(ALPB) compared to experimental values indicating a consistent description of differential solvent effects. Overall, more than twenty solvents for each of the six semiempirical methods are parameterized and tested. They are readily available in the xtb and dftb+ programs for diverse computational applications.

Octanol/water (K OW), octanol/air (K OA), and hexadecane/air (K HdA) partition coefficients are calculated for 67 organic compounds of environmental concern using computational chemistry. The extended CRENSO workflow applied here includes the calculation of extensive conformer ensembles with semiempirical methods and refinement through density functional theory, taking into account solvation models, especially COSMO-RS, and thermostatistical contributions. This approach is particularly advantageous for describing large and nonrigid molecules. With regard to K OW and K HdA, one can refer to many experimental data from direct and indirect measurement methods, and very good matches with results from our quantum chemical workflow are evident. In the case of the K OA values, however, good matches are only obtained for the experimentally determined values. Larger systematic deviations between data computed here and available, nonexperimental quantitative structure–activity relationship literature data occur in particular for phthalic acid esters and organophosphate esters. From a critical analysis of the coefficients calculated in this work and comparison with available literature data, we conclude that the presented quantum chemical composite approach is the most powerful so far for calculating reliable partition coefficients because all physical contributions to the conformational free energy are considered and the structure ensembles for the two phases are generated independently and consistently.

The vapor pressure is a specific and temperature-dependent parameter that describes the volatility of a substance and thus its driving force for evaporation or sublimation into the gas phase. Depending...

Proton transfer reaction rates were calculated for 114 organic compounds using ion–dipole collision theory with quantum mechanically determined dipole moments and polarizabilities.