Conformational Studies of Ortho-and Meta- Isomers and Methyl, Dimethyl, and Chloro Ortho-Substituted Analogues of Dantrolene Using Ab Initio SCF-MO Procedures

摘要

The conformation of the nitro group of nitroaromatic compounds relative to the aromatic ring system is suggested to affect their metabolic activation and mutagenicity. We have recently showed the nitrophenylfuran skeletal muscle relaxant, dantrolene, to be a potent mutagen in Salmonella. Synthesis of ortho-substituted analogues of dantrolene was achieved in an effort to alter the conformation of the nitro group in a manner that will decrease the mutagenicity. Using ab initio techniques we investigated the minimum energy conformation of the nitro group of dantrolene (p-nitro) and its o-and m-nitro isomers as well as the nitro group conformation of dantrolene's ortho- mono- and di- substituted analogues. The most stable conformer for each isomer and analogue was found by optimizing the bond lengths and bond angles for each molecule and rotating about bonds of interest using the STO-3G basis set in the Gaussian-92 program at the Hartree-Fock level.