Structure-mutagenicity relationships in 2-furylethylene derivatives. A molecular orbital study of the role of nitro groups

An analysis of the electronic molecular structure of 2-furylethylene derivatives is carried out using a molecular orbital method. The differences in the electronic features of the nitro groups at two different positions of the furylethylene framework are well-accounted for in the present study. It is shown that nitro groups at position 5 of the furan ring of these compounds are more sensible to reduction in biological media that those at position beta of the exocyclic double bond. This greater sensitivity to reduction of fi-nitro compounds is given by the atomic and group charges on nitro group as well as for the low values of the energy of the lowest unoccupied molecular orbital. Discriminant functions able to classify 2-furylethylenes as mutagenic or not mutagenic are also obtained. These functions permitted the classification of 2-furylethylenes having or not nitro group in their structures. Finally, some quantitative models that describe the mutagenic potency of active compounds in terms of electronic molecular parameters were obtained. In all cases the models developed are in complete agreement with the experimental findings reported for this kind of compounds. (C) 1998 Elsevier Science B.V. All rights reserved.