The conformation of the nitro group of nitroaromatic compounds relative to the aromatic ringsystem is suggested to affect their metabolic activation and mutagenicity. We have recently showed the nitrophenylfuran skeletal muscle relaxant, dantrolene, tobe a potent mutagen inSalmonella. Synthesis of or^o-substituted analogues of dantrolene was achieved in an effort to alter the conformation of the nitro group ina manner that willdecrease the mutagenicity. Using ab initio techniques we investigated the minimum energy conformation of the nitro group of dantrolene (/mitro) and its o-and mnitro 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 ofinterest using the STO-3G basis set in the Gaussian-92 program at the Hartree-Fock level.
Rayburn, Lori L.; Climer, Amber D.; Darsey, Jerry A.; Shaikh, Ali U.; Robertson, Kevin S.; and Fifer, E. Kim
"Conformational Studies of Ortho- and Meto-Isomers and Methyl, Dimethyl, and Chloro Ortho-Substituted Analogues of Dantrolene Using Ab Initio SCF-MO Procedures,"
Journal of the Arkansas Academy of Science: Vol. 49
, Article 30.
Available at: http://scholarworks.uark.edu/jaas/vol49/iss1/30