Structure and thermodynamics of nondipolar molecular liquids and solutions from integral equation theory

Frach, Roland; Heil, Jochen

doi:10.1080/00268976.2016.1167266

Cited by 5 publications

(2 citation statements)

References 71 publications

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“…Relative partition coefficients have been calculated with computer simulations since the late eighties, − whereas absolute partition coefficient calculations have become technically feasible only within the past decade. ,,− The effect of the microheterogeneous structure of wet alcohols was studied by Marcus, as well as Chen and Siepmann. − Also the simulation of the other liquid mixtures has become increasingly relevant. − Lately, the theoretical prediction of physicochemical properties is playing a more important role in industrial applications. ,− …”

Section: Resultsmentioning

confidence: 99%

1-Butanol as a Solvent for Efficient Extraction of Polar Compounds from Aqueous Medium: Theoretical and Practical Aspects

2018

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The extraction of polar molecules from aqueous solution is a challenging task in organic synthesis. 1-Butanol has been used sporadically as an eluent for polar molecules, but it is unclear which molecular features drive its efficiency. Here, we employ free energy simulations to study the partitioning of 15 solutes between water and 1-butanol. The simulations demonstrate that the high affinity of polar molecules to the wet 1-butanol phase is associated with its nanostructure. Small inverse micelles of water are able to accommodate polar solutes and locally mimic an aqueous environment. We verify the simulations based on partition coefficients between water and 1-octanol, and include a blind prediction of the water/1-butanol partition coefficient of cyclohexane-1,2-diol. The calculations are in excellent agreement with experiment, reaching root-mean-square deviations below 0.7 kcal/mol. Actual extractions of cyclohexane-1,2-diol from buffer solutions that mimic cell lysates and suspensions in biocatalytic reactions further exemplify our findings. The yields highlight that extractions with 1-butanol can be significantly more efficient than the conventional protocol based on ethyl acetate.

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Section: Resultsmentioning

confidence: 99%

1-Butanol as a Solvent for Efficient Extraction of Polar Compounds from Aqueous Medium: Theoretical and Practical Aspects

2018

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“…These are applied in the QC calculations from which, after convergence of an iterative cycle, the wave function of the solute in solution as well as the excess chemical potential at infinite dilution and other properties of the fully polarized solute can be determined [12,13]. As usual, we took the sum of the polarized electronic energy and the excess chemical potential as an estimate of the Gibbs energy of the molecule in solution to calculate derived properties such as solvation Gibbs energies (by referencing to a gas phase calculation), acidity constants, partition and distribution coefficients, or tautomer and conformational populations of molecules under ambient and extreme conditions in a variety of solvents [14][15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

The SAMPL6 challenge on predicting octanol–water partition coefficients from EC-RISM theory

Tielker

Tomazic

Eberlein

et al. 2020

J Comput Aided Mol Des

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Results are reported for octanol-water partition coefficients (log P) of the neutral states of drug-like molecules provided during the SAMPL6 (Statistical Assessment of Modeling of Proteins and Ligands) blind prediction challenge from applying the "embedded cluster reference interaction site model" (EC-RISM) as a solvation model for quantum-chemical calculations. Following the strategy outlined during earlier SAMPL challenges we first train 1-and 2-parameter water-free ("dry") and water-saturated ("wet") models for n-octanol solvation Gibbs energies with respect to experimental values from the "Minnesota Solvation Database" (MNSOL), yielding a root mean square error (RMSE) of 1.5 kcal mol −1 for the best-performing 2-parameter wet model, while the optimal water model developed for the pK a part of the SAMPL6 challenge is kept unchanged (RMSE 1.6 kcal mol −1 for neutral compounds from a model trained on both neutral and ionic species). Applying these models to the blind prediction set yields a log P RMSE of less than 0.5 for our best model (2-parameters, wet). Further analysis of our results reveals that a single compound is responsible for most of the error, SM15, without which the RMSE drops to 0.2. Since this is the only compound in the challenge dataset with a hydroxyl group we investigate other alcohols for which Gibbs energy of solvation data for both water and n-octanol are available in the MNSOL database to demonstrate a systematic cause of error and to discuss strategies for improvement.

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The SAMPL5 challenge for embedded-cluster integral equation theory: solvation free energies, aqueous pK a, and cyclohexane–water log D

Tielker

Tomazic

Heil

et al. 2016

J Comput Aided Mol Des

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We predict cyclohexane-water distribution coefficients (log D ) for drug-like molecules taken from the SAMPL5 blind prediction challenge by the "embedded cluster reference interaction site model" (EC-RISM) integral equation theory. This task involves the coupled problem of predicting both partition coefficients (log P) of neutral species between the solvents and aqueous acidity constants (pK) in order to account for a change of protonation states. The first issue is addressed by calibrating an EC-RISM-based model for solvation free energies derived from the "Minnesota Solvation Database" (MNSOL) for both water and cyclohexane utilizing a correction based on the partial molar volume, yielding a root mean square error (RMSE) of 2.4 kcal mol for water and 0.8-0.9 kcal mol for cyclohexane depending on the parametrization. The second one is treated by employing on one hand an empirical pK model (MoKa) and, on the other hand, an EC-RISM-derived regression of published acidity constants (RMSE of 1.5 for a single model covering acids and bases). In total, at most 8 adjustable parameters are necessary (2-3 for each solvent and two for the pK) for training solvation and acidity models. Applying the final models to the log D dataset corresponds to evaluating an independent test set comprising other, composite observables, yielding, for different cyclohexane parametrizations, 2.0-2.1 for the RMSE with the first and 2.2-2.8 with the combined first and second SAMPL5 data set batches. Notably, a pure log P model (assuming neutral species only) performs statistically similarly for these particular compounds. The nature of the approximations and possible perspectives for future developments are discussed.

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Structure and thermodynamics of nondipolar molecular liquids and solutions from integral equation theory

Cited by 5 publications

References 71 publications

1-Butanol as a Solvent for Efficient Extraction of Polar Compounds from Aqueous Medium: Theoretical and Practical Aspects

1-Butanol as a Solvent for Efficient Extraction of Polar Compounds from Aqueous Medium: Theoretical and Practical Aspects

The SAMPL6 challenge on predicting octanol–water partition coefficients from EC-RISM theory

The SAMPL5 challenge for embedded-cluster integral equation theory: solvation free energies, aqueous pK a, and cyclohexane–water log D

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