A correlation for 1,9-decadiene/water partition coefficients.

Area of Science:

• Pharmacokinetics and Drug Discovery
• Computational Chemistry
• Membrane Biophysics

Background:

• The 1,9-decadiene/water partition coefficient (K(decadiene/w)) is a key predictor of molecular bioavailability and phospholipid bilayer membrane permeability.
• Existing datasets for K(decadiene/w) are limited, hindering accurate bioavailability predictions.

Purpose of the Study:

• To develop an optimal quantitative structure-property relationship (QSPR) model for predicting log(10) K(decadiene/w).
• To assess the contribution of K(decadiene/w) prediction error to overall membrane permeability models.

Main Methods:

• Utilized a 58-point dataset of K(decadiene/w) values.
• Developed a predictive model using the octanol/water partition coefficient and four Abraham solvation parameters (A, S, E, V).
• Evaluated model performance using root-mean-square error (RMSE) and probable error.

Main Results:

• Achieved a root-mean-square error of 0.42 for the fitted dataset.
• The probable error for new compounds is estimated at 0.49.
• The uncertainty in K(decadiene/w) prediction was identified as the dominant error source in a companion phospholipid bilayer permeability model.

Conclusions:

• The developed QSPR model provides a reliable method for predicting K(decadiene/w).
• Improving K(decadiene/w) prediction accuracy is critical for advancing phospholipid bilayer membrane permeability models.
• Expansion of the experimental K(decadiene/w) database is recommended to enhance predictive accuracy.