. . . . . . . . 7 1. 6. AValidated(Q)SARoraValidPrediction? . . . . . . . . . . . . . . . . . . 9 1. 7. UsinginSilicoTechniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 1. 8. NewAreasforinSilicoModels. . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 1. 9. Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 2 TheUseofQuantumMechanicsDerivedDescriptorsin ComputationalToxicology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Steven J. Enoch 2. 1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 2. 2. TheSchrödingerEquation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 2. 3. Hartree¿FockTheory. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 2. 4. Semi-EmpiricalMethods:AM1andRM1. . . . . . . . . . . . . . . . . . . . 18 2. 5. ABInitio:DensityFunctionalTheory. . . . . . . . . . . . . . . . . . . . . . . 19 2. 6. QSARforNon-ReactiveMechanismsofAcute(Aquatic) Toxicity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 2. 7. QSARsforReactiveToxicityMechanisms. . . . . . . . . . . . . . . . . . . 21 2. 7. 1. AquaticToxicityandSkinSensitisation. . . . . . . . . . . . . 21 2. 7. 2. QSARsforMutagenicity . . . . . . . . . . . . . . . . . . . . . . . . . 24 2. 8. FutureDirectionsandOutlook. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 2. 9. Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 vii viii Contents 3 MolecularDescriptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Vi

An interdisciplinary overview on recent advances in Quantitative Structure-Activity Relationships (QSAR) studies

Part I Theory of QSAR 1 Quantitative Structure-Acticity Relationships (QSAR) ¿ Applications and MethodologyMark T. D. Cronin 2 The Use of Quantum Mechanics Derived Descriptors in Computational ToxicologySteven J. Enoch 3 Molecular DescriptorsViviana Consonni, Roberto Todeschini 4 3D-QSAR ¿ Applications, Recent Advances and LimitationsWolfgang Sippl 5 Virtual Screening and Molecular Design Based on Hierarchical QSAR TechnologyVictor E. Kuz¿min, A. G. Artemenko, Eugene N. Muratov, P. G. Polischuk, L. N. Ognichenko, A. V. Liahovsky, A. I. Hromov, E. V. Varlamova 6 Robust Methods in QSARMichal Daszykowski, Ivana Stanimirova, Beata Walczak 7 Chemical Category Formation and Read Across for the Prediction of ToxicitySteven J. Enoch Part II Practical Applications 8 QSAR in Chromatography: Quantitative Structure-Retention Relationships (QSRR)Roman Kaliszan, Tomasz Baczek 9 The Use of QSAR and Computational Methods in Drug DesignFania Bajot 10 In Silico Approaches for Predicting ADME PropertiesJudith C. Madden 11 Prediction of Harmful Human Health Effects of Chemicals from StructureMark T.D. Cronin 12 Chemometric Methods and Theoretical Molecular Descriptors in Predictive QSAR Modeling of the Environmental Behaviour of Organic PollutantsPaola Gramatica 13 The Role of QSAR Methodology in the Regulatory Assessment of ChemicalsAndrew P. Worth 14 Nanomaterials ¿ the Next Great Challenge for QSAR ModelersTomasz Puzyn, Agnieszka Gajewicz, Danuta Leszczynska, Jerzy Leszczynski