COSMO-RS blind prediction of distribution coefficients and aqueous pKa values from the SAMPL8 challenge.

The SAMPL8 blind prediction challenge, which addresses the acid/base dissociation constants (pKa) and the distribution coefficients (logD), was addressed by the Conductor like Screening Model for Realistic Solvation (COSMO-RS). Using the COSMOtherm implementation of COSMO-RS together with a rigorous conformational sampling, yielded logD predictions with a root mean square deviation (RMSD) of 1.36 log units over all 11 compounds and seven bi-phasic systems of the data set, which was the most accurate of all contest submissions (logD).

Quantifying Uncertainties in Solvation Procedures for Modeling Aqueous Phase Reaction Mechanisms.

Computational quantum chemistry provides fundamental chemical and physical insights into solvated reaction mechanisms across many areas of chemistry, especially in homogeneous and heterogeneous renewable energy catalysis. Such reactions may depend on explicit interactions with ions and solvent molecules that are nontrivial to characterize. Rigorously modeling explicit solvent effects with molecular dynamics usually brings steep computational costs while the performance of continuum solvent models such as polarizable continuum model (PCM), charge-asymmetric nonlocally determined local-electric (CANDLE), conductor-like screening model for real solvents (COSMO-RS), and effective screening medium method with the reference interaction site model (ESM-RISM) are less well understood for reaction mechanisms.

Prediction of cyclohexane-water distribution coefficients with COSMO-RS on the SAMPL5 data set.

The Conductor-Like-Screening-Model for Real Solvents (COSMO-RS) method has been used for the blind prediction of cyclohexane-water distribution coefficients logD within the SAMPL challenge. The partition coefficient logP of the neutral species was calculated first and then corrected for dissociation or protonation, as appropriate for acidic or basic solutes, to obtain the cyclohexane-water logD. Using the latest version of the COSMOtherm implementation, this approach in combination with a rigorous conformational sampling yielded a predictive accuracy of 2.

Interpretation of experimental hydrogen-bond enthalpies and entropies from COSMO polarisation charge densities.

In this work, experimental hydrogen-bond (HB) enthalpies measured in previous works for a wide range of acceptor molecules in dilute mixtures of 4-fluorophenol in non-polar solvents are quantified from COSMO polarisation charge densities σ of HB acceptors (HBA). As well as previously demonstrated for quantum chemically calculated HB enthalpies, a good correlation of the experimental data with the polarisation charge densities is observed, covering an extended range of HBA (O, N, S, π systems and halogens) ranging from very weak to strong hydrogen bonds. Furthermore, for the first time, a quantitative analysis of experimental HB entropies is performed for such a chemical diversity of HBA.

Polarization charge densities provide a predictive quantification of hydrogen bond energies.

A systematic density functional theory based study of hydrogen bond energies of 2465 single hydrogen bonds has been performed. In order to be closer to liquid phase conditions, different from the usual reference state of individual donor and acceptor molecules in vacuum, the reference state of donors and acceptors embedded in a perfect conductor as simulated by the COSMO solvation model has been used for the calculation of the hydrogen bond energies. The relationship between vacuum and conductor reference hydrogen bond energies is investigated and interpreted in the light of different physical contributions, such as electrostatic energy and dispersion.

COSMO-RS: an alternative to simulation for calculating thermodynamic properties of liquid mixtures.

The conductor-like screening model for realistic solvation (COSMO-RS) method has been established as a novel way to predict thermophysical data for liquid systems and has become a frequently used alternative to force field-based molecular simulation methods on one side and group contribution methods on the other. Through its unique combination of a quantum chemical treatment of solutes and solvents with an efficient statistical thermodynamics procedure for the molecular surface interactions, it enables the efficient calculation of many properties that other methods can barely predict. This review presents a short delineation of the theory, the application potential and limitations of COSMO-RS, and its most important application areas.

Prediction of the free energy of hydration of a challenging set of pesticide-like compounds.

In a blind validation test the COSMO-RS method, a combination of the quantum chemical dielectric continuum solvation model COSMO with a statistical thermodynamics treatment for more realistic solvation (RS) simulations, has been used for the direct prediction of transfer free energies of 55 demanding pesticide-like compounds. Comparison with experimental data yields an rms deviation of approximately 2 kcal/mol, which is in the order of the estimated inaccuracy of the experimental data. A detailed comparison reveals experimental and calculation pitfalls on conformational flexible, multifunctional, polar compounds.

Prediction of acidity in acetonitrile solution with COSMO-RS.

The COSMO-RS method, a combination of the quantum chemical dielectric continuum solvation model COSMO with a statistical thermodynamics treatment for realistic solvation simulations, has been used for the prediction of pK(a) values in acetonitrile. For a variety of 93 organic acids, the directly calculated values of the free energies of dissociation in acetonitrile showed a very good correlation with the pK(a) values (r(2) = 0.97) in acetonitrile, corresponding to a standard deviation of 1.

Probing carboxylate Gibbs transfer energies via liquid|liquid transfer at triple phase boundary electrodes: ion-transfer voltammetry versus COSMO-RS predictions.

Understanding liquid|liquid ion transfer processes is important in particular for naturally occurring species such as carboxylates. In this study electrochemically driven mono-, di-, and tri-carboxylate anion transfer at the 4-(3-phenylpropyl)pyridine|aqueous electrolyte interface is investigated experimentally for a triple phase boundary system at graphite electrodes. The tetraphenylporphyrinato-Mn(III/II) redox system (Mn(III/II)TPP) dissolved in the water-immiscible organic phase (4-(3-phenylpropyl)pyridine) is employed for the quantitative study of the structure-Gibbs transfer energy correlation and the effects of the solution pH on the carboxylate transfer process.

Accurate prediction of basicity in aqueous solution with COSMO-RS.

The COSMO-RS method, a combination of the quantum chemical dielectric continuum solvation model COSMO with a statistical thermodynamics treatment for realistic solvation simulations, has been used for the prediction of base pK(a) constants. For a variety of 43 organic bases the directly calculated values of the free energies of dissociation in water showed a very good correlation with experimental base pK(a) values (r2 = 0.98), corresponding to a standard deviation of 0.

Application of the conductor-like screening model for real solvents for prediction of the aqueous solubility of chlorobenzenes depending on temperature and salinity.

The conductor-like screening model for real solvents (COSMO-RS) is applied to the prediction of the aqueous solubility of chlorobenzenes (CBZs) in a liquid-liquid and liquid-solid equilibrium. The solubilities of CBZs at temperatures ranging from 5 to 60 degrees C are reported, and the enthalpies of solution are derived from van't Hoff plots. The salting effect of 12 chlorobenzenes is determined for sodium, potassium, and calcium solutions at concentrations ranging from 0.

First Principles Calculations of Aqueous pKa Values for Organic and Inorganic Acids Using COSMO-RS Reveal an Inconsistency in the Slope of the pKa Scale.

The COSMO-RS method, a combination of the quantum chemical dielectric continuum solvation model COSMO with a statistical thermodynamics treatment for more realistic solvation (RS) simulations, has been used for the direct prediction of pKa constants of a large variety of 64 organic and inorganic acids. A highly significant correlation of r(2) = 0.984 with a standard deviation of only 0.

Prediction of soil sorption coefficients with a conductor-like screening model for real solvents.

Using a general theory for partition coefficients based on a quantum chemically derived conductor-like screening model for real solvents sigma-moment descriptors, the logarithmic soil sorption coefficients log K(oc) of a database of 440 compounds has been successfully correlated, achieving a standard deviation (root-means-squared [RMS]) of 0.62 log-units on the training set and a predictive RMS of 0.72 log-units on a more demanding test set.

A comparison between the two general sets of linear free energy descriptors of Abraham and Klamt.

Two sets of molecular descriptors, the five experimental Abraham, and the five COSMOments of Klamt's COSMO-RS, have been compared for a data set of 470 compounds. Both sets are considered as almost complete sets of LFER. The two sets of descriptors are shown to exhibit a large overlap as far as their chemical content.

Prediction of aqueous solubility of drugs and pesticides with COSMO-RS.

The COSMO-RS method, originally developed for the prediction of liquid-liquid and liquid-vapor equilibrium constants based on quantum chemical calculations, has been extended to solid compounds by addition of a heuristic expression for the Gibbs free energy of fusion. By this addition, COSMO-RS is now capable of a priori prediction of aqueous solubilities of a wide range of typical neutral drug and pesticide compounds. Only three parameters in the heuristic expression have been fitted on a data set of 150 drug-like compounds.