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Quantification of the Membrane Toxicity of Hydrophobic Ionogenic Organic Compounds (Hiocs): Role of Uptake and Speciation for Single Compounds and Binary Mixtures

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Quantification of the Membrane Toxicity of Hydrophobic Ionogenic Organic Compounds (Hiocs): Role of Uptake and Speciation for Single Compounds and Binary Mixtures Diss. ETH No. 14066 Quantification of the membrane toxicity of hydrophobic ionogenic organic compounds (HIOCs): Role of uptake and speciation for single compounds and binary mixtures René W. Hunziker Zürich, 2001 Diss. ETH No. 14066 Quantification of the membrane toxicity of hydrophobic ionogenic organic compounds (HIOCs): Role of uptake and speciation for single compounds and binary mixtures A dissertation submitted to the Swiss Federal Institute of Technology Zürich for the degree of Doctor of Natural Sciences Presented by René W. Hunziker Dipl. Natw. ETH born October 10th, 1968 citizen of Moosleerau (AG) Accepted on the recommendation of Prof. Dr. R.P. Schwarzenbach, examiner Prof. Dr. U.P. Fringeli, co-examiner Dr. R. Altenburger, co-examiner Dr. B.I. Escher, co-examiner Zürich, 2001 Table of contents Summary............................................................................................................................................. VII Zusammenfassung............................................................................................................................ IX 1. General introduction................................................................................................................... 1 1.1 Biomembranes as site of toxic action................................................................................. 2 1.2 Membrane toxicity of hydrophobic ionogenic organic compounds (HIOC) .............. 4 1.3 Objectives............................................................................................................................... 6 1.4 Outline.................................................................................................................................... 7 2. The pH dependence of the partitioning of triphenyltin and tributyltin between phosphatidylcholine liposomes and water............................................................................. 9 2.1 Introduction........................................................................................................................... 10 2.2 Materials and methods........................................................................................................ 12 2.2.1 Chemicals .................................................................................................................12 2.2.2 Aqueous solutions .................................................................................................. 12 2.2.3 Preparation of liposomes....................................................................................... 12 2.2.4 Determination of liposome-water and chromatophore-water distribution ratios of tributyltin and triphenyltin............................................. 13 2.2.5 Analytical procedures ............................................................................................ 14 2.2.6 Calculation of triorganotin concentrations in the liposomes ........................... 15 2.3 Results and discussion......................................................................................................... 16 2.3.1 Liposome-water partitioning ................................................................................ 16 2.3.2 Chromatophore-water partitioning ..................................................................... 21 2.4 Conclusion............................................................................................................................. 22 3. Acute toxicity of triorganotin compounds: Different specific effects on the energy metabolism and role of pH........................................................................................... 23 3.1 Introduction........................................................................................................................... 24 3.1.1 Effects of tinorganic compounds on the energy metabolism of cells.............. 24 3.2 Materials and methods........................................................................................................ 28 3.2.1 Chemicals .................................................................................................................28 3.2.2 Stock solutions......................................................................................................... 28 3.2.3 Preparation of the chromatophores ..................................................................... 29 3.2.4 Protonophoric shuttle and bc1 complex inhibition............................................. 29 3.2.5 ATP synthesis inhibition........................................................................................ 30 3.2.6 Definition of the nominal chromatophore concentration, ccph,nom ..................... 31 3.3 Results and discussion......................................................................................................... 32 3.3.1 Inhibition of the bc1 complex ................................................................................. 32 – III – 3.3.2 Comparison of OH–/Cl– antiport and OH– uniport ........................................... 33 3.3.3 OH– uniport ............................................................................................................. 33 3.3.4 Inhibition of ATP synthesis ................................................................................... 38 3.3.5 Comparison of the different mechanisms of action ........................................... 39 4. Interaction of phenolic uncouplers in binary mixtures: Concentration-additive and synergistic effects ................................................................................................................. 41 4.1 Introduction........................................................................................................................... 42 4.2 Material and methods .......................................................................................................... 44 4.2.1 Chemicals .................................................................................................................44 4.2.2 Determination of the uncoupling activity ........................................................... 44 4.2.3 Experiments with single compounds................................................................... 45 4.2.4 Experiments with binary mixtures ....................................................................... 45 4.2.5 Physicochemical parameters ................................................................................. 46 4.3 Quantitative evaluation and representation of the experimental data......................... 46 4.4 Results and discussion ......................................................................................................... 48 4.4.1 Evaluation of the mixed dimer model ................................................................. 48 4.4.2 Effect of pH............................................................................................................... 54 4.4.3 Effect of substitution pattern ................................................................................. 55 4.4.4 Comparison with concentration addition............................................................ 56 4.4.5 Comparison with data from literature ................................................................. 58 4.4.6 Significance for environmental risk assessment of mixtures............................ 61 5. General discussion and conclusions ........................................................................................ 63 References........................................................................................................................................... 67 Appendix A: The energy-transducing membran of R. sphaeroides and the derivation of the uncoupling activity by time-resolved spectroscopy ............................................................. 77 Chromatophores of R. sphaeroides as model for energy-transducing membranes........................................................................................................................... 78 Determination of build-up and decay kinetics of the membrane potential with time-resolved spectroscopy ..................................................................................... 80 Deduction of the uncoupling activity .............................................................................. 82 References ............................................................................................................................ 85 Appendix B: Kinetic model to describe the intrinsic uncoupling activity of substituted phenols in energy transducing membranes............................................................................ 87 Acknowledgments ............................................................................................................................ 100 Curriculum Vitae............................................................................................................................... 101 – IV – Tables Table 2.1: pKa, liposome-water, chromatophore-water, and octanol-water distribution ratios of tributyltin and triphenyltin.................................................. 19 Table 4.1 Physicochemical parameters of phenolic uncouplers and anisols ...................... 50 Table 4.2 Uncoupling activities of the single phenolic uncouplers and anisols at various pH values..................................................................................................
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