title: Prediction of immobilised artificial membrane chromatography retention factors using theoretical molecular fragments and structural features.
abstract: Many in silico alternatives to aquatic toxicity tests rely on hydrophobicity-based quantitative structure-activity relationships (QSARs). Hydrophobicity is often estimated as log P, where P is the octanol-water partition coefficient. Immobilised artificial membrane (IAM) high performance liquid chromatography (HPLC) may be a more biologically relevant alternative to log P. The aim of this study was to investigate the applicability of a theoretical structural fragment and feature-based method to predict log k IAM (the logarithm of the retention index determined by IAM-HPLC) values. This will allow the prediction of log k IAM based on chemical structure alone. The use of structural fragment values to predict log P was first proposed in the 1970s. The application of a similar method using fragment values to predict log k IAM is a novel approach. Values of log k IAM were determined for 22 aliphatic and 42 aromatic compounds using an optimised and robust IAM-HPLC assay. The method developed shows good predictive performance using leave-one-out cross validation and application to an external validation set not seen a priori by the training set also generated good predictive values. The ability to predict log k IAM without the need for practical measurement will allow for the increased use of QSARs based on this descriptor.
authors.affiliation: School of Pharmacy and Chemistry, Liverpool John Moores University, United Kingdom. Moira.Ledbetter@unilever.com
authors.forename: M R
authors.initials: MR
authors.lastname: Ledbetter
authors.forename: S
authors.initials: S
authors.lastname: Gutsell
authors.forename: G
authors.initials: G
authors.lastname: Hodges
authors.forename: S
authors.initials: S
authors.lastname: O'Connor
authors.forename: J C
authors.initials: JC
authors.lastname: Madden
authors.forename: P H
authors.initials: PH
authors.lastname: Rowe
authors.forename: M T D
authors.initials: MT
authors.lastname: Cronin
mesh_terms: D002851:Chromatography, High Pressure Liquid; D057927:Hydrophobic and Hydrophilic Interactions; D008567:Membranes, Artificial; D015394:Molecular Structure; D009930:Organic Chemicals / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D008567:Membranes, Artificial; D009930:Organic Chemicals