QSAR model for the prediction of bio-concentration factor using aqueous solubility and descriptors considering various electronic effects

Abstract

The in silico modelling of bio-concentration factor (BCF) is of considerable interest in environmental sciences, because it is an accepted indicator for the accumulation potential of chemicals in organisms. Numerous QSAR models have been developed for the BCF, and the majority utilize the octanol/water partition coefficient (log P) to account for the penetration characteristics of the chemicals. The present work used descriptors from a variety of software packages for the development of a multi-linear regression model to estimate BCF. The modelled data set of 473 diverse compounds covers a wide range of log BCF values. In the proposed QSAR model, most of the variation is described by the calculated solubility in water. Other contributing descriptors describe, for instance, hydrophobic surface area, hydrogen bonding and other electronic effects. The model was validated internally by using a variety of statistical approaches. Two external validations were also performed. For the former validation, a subset from the same data source was used. The 2nd external validation was based on an independent data set collected from different resources. All validations showed the consistency of the model. The applicability domain of the model was discussed and described and a thorough outlier analysis was performed.

Keywords:

• bioconcentration
• BCF
• QSAR
• solubility
• applicability domain

Acknowledgement

Estonian Ministry for Education and Research (grant SF0140031Bs09), Estonian Science Foundation (grants 7153 & 7709), and EU 6th FP project Chemomentum (IST-033437).