PARENT SESSION

1F - QSAR
Hall 13
8:30 AM - 12:30 PM, Tuesday, 29 April 2003
Chair: Schüürmann, G.¹, ¹
Co-chair: Verhaar, H.J.M.², Cronin, M.³, ^{2 3}

(TU13/3) Structure-Toxicity Relationships for ,-Unsaturated Aliphatic Chemicals.

Cronin, Mark¹, Netzeva, Tatiana¹, Sinks, Glendon², Schultz, Terry², ¹ Liverpool John Moores University, Liverpool, Merseyside, England² The University of Tennessee, Knoxville, TN, USA

ABSTRACT- ,-Unsaturated aliphatic chemicals are typically characterised as acting as Michael-type acceptors, however, the ability to develop QSARs for, and hence model, their toxicity has met with limited success. In this study, toxicity was assessed in the Tetrahymena pyriformis population growth impairment assay. The potency (log (IGC₅₀^-1)) of most chemicals was in excess of baseline narcosis as quantified by the 1-octanol/water partition coefficient (log K_ow). Efforts to model these molecules with a wide variety of descriptors within a single domain (i.e. as a single chemical class) were unsuccessful. ,-Unsaturated aldehydes were well modelled by the incorporation a molecular connectivity index (^3v_PC), to account for branching, with log K_ow [log (IGC₅₀^-1) = 0.480 (log K_ow) - 1.344 (^3v_PC) + 0.058; n = 17, r² = 0.840, s = 0.227]. Methacrylates were modelled by log K_ow and the energy of the lowest unoccupied molecular orbital (E_lumo) [log (IGC₅₀^-1) = 0.536 (log K_ow) - 8.90 (E_lumo) - 0.993; n = 11, r² = 0.816, s = 0.284]. Acrylates, following the removal of several outliers, were modelled by the frontier orbital-related parameter maximum superdelocalizability (A_max), the size/shape term was shape flexibility (ShapeFlex), and two indicator variables representing whether the ,-unsaturated substructure was embedded within or at an end of the molecule (I_in/out) and whether the molecule was an ester or a ketone (I_est/ket). An additional group of ,-unsaturates were those having a double polarised or an ,,- triple unsaturated moiety. These compounds were modelled by E_lumo in conjunction with an indicator variable (I_dub/trip) for the double or triple moiety.

Key words: QSAR, toxic mechanisms, aquatic systems, organics