title: Quantitative structure-activity relationship modeling of acute toxicity of quaternary alkylammonium sulfobetaines to Daphnia magna.
abstract: The logarithm of the octanol/water partition coefficient has been widely used as the sole physicochemical property to define various types of biological activity, such as aquatic toxicity. In the present study, we derive a quantitative structure-activity relationship (QSAR) equation for the prediction of acute aquatic toxicity (48-h median effective concentration) of quaternary alkylammonium sulfobetaines to the aquatic invertebrate Daphnia magna Straus. The single-parameter approach described is also based on the hydrophobicity parameter, log P. The 17 zwitterionic compounds were considered for QSAR development. They have the general formula RN+(CH3)2(CH2)nSO3-, where n = 2 to 4, and were synthesized by reacting the corresponding N,N-dimethylamines with either sodium-2-chloroethanesulfonate (n = 2), 1,3-propanesultone (n = 3), or 1,4-butanesultone (n = 4). The R group was either a C6 to C12 alkyl chain, a phenylalkyl unit bearing a C1 to C4 chain, or a phenylpropyl unit with a C4 to C6 para-substituted alkyl group. Octanol/water partition coefficients were experimentally determined via a conventional stir-flask procedure, which was quantified using a reverse-phase, high-performance liquid chromatographic technique coupled with either an ultraviolet or an electrospray ionization mass spectrometry detection system. Median effective concentration values were also determined experimentally via a standard acute immobilization test recommended by Organisation for Economic Cooperation and Development (Paris, France) Guideline 202. The established QSAR equation for such zwitterionic compounds is consistent with the standard equation that normally defines the polar narcosis mode of toxic action.
authors.affiliation: University of Wales Swansea, Singleton Park, Swansea SA2 8PP, United Kingdom. jodavies23@hotmail.com
authors.forename: Joanna
authors.initials: J
authors.lastname: Davies
authors.forename: Robert S
authors.initials: RS
authors.lastname: Ward
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Hodges
authors.forename: David W
authors.initials: DW
authors.lastname: Roberts
mesh_terms: D000818:Animals; D001622:Betaine / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis / Q000633:toxicity*; D003621:Daphnia / Q000187:drug effects*; D057927:Hydrophobic and Hydrophilic Interactions; D008954:Models, Biological; D000442:Octanols; D021281:Quantitative Structure-Activity Relationship; D000644:Quaternary Ammonium Compounds / Q000032:analysis / Q000138:chemical synthesis / Q000633:toxicity*; D012995:Solubility; D013501:Surface-Active Agents / Q000032:analysis / Q000138:chemical synthesis / Q000633:toxicity; D023382:Toxicity Tests, Acute / Q000379:methods*; D014867:Water
chemical_list: D000442:Octanols; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; D014867:Water; D001622:Betaine; C483727:sulfobetaine