Quantitative structure-activity relationship modeling of acute toxicity of quaternary alkylammonium sulfobetaines to Daphnia magna.

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.

Applications of immobilised artificial membrane chromatography to quaternary alkylammonium sulfobetaines and comparison of chromatographic methods for estimating the octanol-water partition coefficient.

The chromatographic behaviour of a series of quaternary alkylammonium sulfobetaines of general formula RN-(CH3)2(CH2)nSO3-, where n = 2-4, has been examined using an immobilised artificial membrane column. The k values have been correlated both with experimentally determined values for the octanol-water partition coefficient (P) and with aquatic toxicity measurements. Other indirect chromatographic methods for measuring log P for these compounds using reversed-phase columns and octanol-coated columns have also been investigated.