Acta Chimica Slovaca (ACS) publishes papers on fundamental and applied aspects of chemistry, biochemistry, chemical technology, chemical engineering and process control, biotechnology and food technology. Welcome are also topics which include chemical aspects of materials, physical chemistry and chemical physics, analytical chemistry, macromolecular chemistry and biomedical engineering.

Comparison of parametric methods with quantum mechanics based models to estimate Clog P values

Dávid Zajaček *, Andrej Hlinčík, Lukas Bucinsky, Matej Uhliar

Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37 Bratislava, Slovakia

E-mail: * david.zajacek@stuba.sk

Abstract:

The logarithm of octanol-water partition coefficient (log P) is estimated by means of six parametric
methods (iLOGP, XLOGP3, WLOGP, MLOGP, SILICOS-IT, OBLogP) and six quantum mechanics (QM)
based models. QM models comprise DFT functional choice (B3LYP, M06-X, PBE0, including the xTB
parametrization variant), implicit solvent model choice (IEFPCM, SMD, or ALPB), and basis set quality in
DFT calculations (6-31G* and 6-311++G**). Several statistics are evaluated to compare Clog P estimates to
experimentally measured dataset of 36 molecules picked from Meylan and Howard J. Pharm. Sci. 84 (1995)
83—92. ChemmineR cluster analysis has been performed to confirm structural diversity of molecules in the
employed molecular dataset. XLOGP3 performance is the best among all the methods used, while SMD based
DFT models showed a clearly competitive results with the remaining parametric methods irrespective of DFT
functional or basis set quality.

Keywords: log P, parametric methods, XLOGP3, density functional theory, implicit solvent model, SMD

Acta Chimica Slovaca, Vol. 18, No. 1, 2025, pp. 8—23, DOI: 10.2478/acs-2025-0002