Development of QSARs to investigate the bacterial toxicity and biotransformation potential of aromatic heterocylic compounds

A series of aromatic heterocyclic and hydrocarbon compounds were tested for toxicity and biotransformation potential against two contrasting lux-marke d whole-cell microbial biosensors. Toxicity was determined by inhibition of light output of a Pseudomonas fluorescens construct that expresses lux con stitutively. Biotransformation was tested by increase in light output of P. flourescens HK44 (pUTK21), which expresses lux when in the presence of a m etabolic intermediate (salicylate). The data were then modelled against phy sical/chemical properties of the compounds tested to see if quantitative st ructure-activity relationships (QSARs) could be derived. Toxicity was found to be accurately predicted by log K-ow (R-2 = 0.95, Q(2) = 0.88), with the basic (pyridine-ring containing) heterocycles modelled separately. The bio transformation data were best modelled using lowest unoccupied molecular or bital (LUMO) energies (R-2 = 0.90, Q(2) = 0.87). (C) 2001 Elsevier Science Ltd. All rights reserved.