Predicting Relative Stability of Conformers in Solution with COSMO-RS

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Vol. 121; no. 36; pp. 6823 - 6829
• Main Authors: Pung, Astrid, Leito, Ivo
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 14.09.2017
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/acs.jpca.7b05197

The ability of the COSMO-RS method to predict the relative stability of different conformers of the same species in solution was evaluated by comparing computational results with experimental conformer data for 105 molecules from 20 literature sources. The solvents CDCl3, CD2Cl2, benzene, toluene, ethyl ether, tetrahydrofuran, acetone, dimethyl­formamide, DMSO (and DMSO-d 6), water, and ethanol were used (dictated by the solvents used in the literature). In the case of 16 molecules the quantitative conformer abundances were also available and were compared with the data from computations. The results show that although COSMO-RS reproduces the conformer abundances only very approximately, the most stable conformer is determined correctly in 103 cases out of 105. This result validates the use of COSMO-RS in a number of applications (distribution coefficients, vapor pressures, solubilities, etc.) where the most stable conformer of a molecule can be different in different phases and accounting for this difference is important for obtaining meaningful results.