Introduction

 

Compounds having ionizable groups exist in solution as a mixture of different ionic forms. The ionization of those groups, thus the ratio of the ionic forms depends on the pH. Since loP describes the hydrophobicity of one form only, the apparent logP value can be different. The logD represents the octanol-water coefficient of compounds at a given pH value.

Learn more about how the logD Plugin works.

The result window shows the pH:logD curves for each molecule drawn in the sketcher. The molecule images are shown in the legend. When clicking on an image, the corresponding molecule is displayed in the upper-left part of the panel.

The reference logD values originally shown can be reached by either clicking on the chart outside of the legend image areas or else by selecting logD at reference pHs from the View menu.

 

Fig. 1 logD result window showing the logD-pH curves for three molecules

Options

General Options

 

Different calculation (prediction) options can be set in the General Options tab of the logD Options window:

 

• logP Method
  • VG: the calculation method derived from Viswanadhan et al. is applied.
  • KLOP: logP data from Klopman et al. is applied.
  • PHYSPROP: logP data from PHYSPROP^© database is used.
  • User defined: if a training set of structures and corresponding experimental logP values is created by the user (and stored in the appropriate format), it can be used for training logP calculations. See this document about creating such sets.
  • Weighted: this is the default setting. Available calculation methods can be combined with different weights. Selecting this method turns the Method weights section active.
• LogP Training ID: if the User defined or the Weighted method is selected, this dropdown list becomes active. All created training sets are listed here. Choose the one to apply for the calculation. Read more on creating a training set.
• Method weights: you can set the proportion of the methods used in the calculations. Acitve only in Weighted method.
• Electrolyte concentration
  • Cl^- concentration: can be set between 0.1 and 0.25 mol/L.
  • Na⁺ K⁺ concentration: can be set between 0.1 and 0.25 mol/L.
• pKa correction library: the custom pKa training for the compounds may be used. First, create a training set for your compunds, which then will appear in the dropdown list. If the option is checked, this list becomes active. Read more on creating a training set.
• Consider tautomerization: in case of tautomer structures, all dominant tautomers at given pH are taken into account during the logD calculation.

 

 Fig. 2 General Options tab of the logD Options window

Display Options

 

Different display options can be set in the Display Options tab of the logD Options panel:

• Precision: setting the number of decimal places with which the result value is given.
• Chart: pH limits, pH step size: defines the pH window in which the logD is calculated, with pH values starting from the lower limit incremented by the step size, the results given in table format and a chart.
• Reference pH values: the logD at the given reference pH values are calculated, both pH and logD values with the predefined accuracy.

 

Fig. 3 Display Options tab of the logD Options window

References

1. Viswanadhan, V. N.; Ghose, A. K.; Revankar, G. R.; Robins, R. K., J. Chem. Inf. Comput. Sci., 1989, 29, 163-172; doi
2. Klopman, G.; Li, Ju-Yun.; Wang, S.; Dimayuga, M.: J.Chem.Inf.Comput.Sci., 1994, 34, 752; doi
3. PHYSPROP^© database
4. Csizmadia, F; Tsantili-Kakoulidou, A.; Pander, I.; Darvas, F., J. Pharm. Sci., 1997, 86, 865-871; doi