Associations of the bacterial mutagenicity of halogenated 2(5H)-furanones with their MNDO-PM3 computed properties and mode of reactivity with sodium borohydride

• Published in: Chemical research in toxicology 1992-05, Vol.5 (3), p.392-400
• Main Authors: LaLonde, Robert T, Leo, Howard, Perakyla, Hannu, Dence, Carlton W, Farrell, Robert P
• Format: Article
• Language: English
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - chemistry; 4-Butyrolactone - toxicity; Animals; Biological and medical sciences; Borohydrides - chemistry; Chemical mutagenesis; Chemical Phenomena; Chemistry, Physical; In Vitro Techniques; Magnetic Resonance Spectroscopy; Medical sciences; Mutagenicity Tests; Mutagens - chemistry; Mutagens - toxicity; Rats; Salmonella typhimurium - drug effects; Salmonella typhimurium - growth & development; Toxicology
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx00027a012

Electrophilicity as a general basis for both the mutagenicity and nucleophile inactivation of halogen-substituted 2(5H)-furanones was tested. Lowest unoccupied molecular orbital (LUMO) energy levels and stabilities of 2(5H)-furanone radical anions and C-2, C-3, and C-4 anionic hydride adducts were computed with MNDO-PM3 for each of 10 compounds. These three computed sets of values were considered electrophilicity indicators. Each individual value from a given indicator set was plotted against the logarithm of the Salmonella typhimurium (TA100) mutagenicities (log Mm) for each of the corresponding compounds. Highest occupied molecular orbital (HOMO) energy levels for the 10 compounds were also computed. Strong negative correlations were obtained from the plots of LUMO and radical anion stability against log Mm of the 10 compounds. Also, a negative correlation was observed for the plot of the stability of the C-4 anionic hydride adduct for a smaller set of six compounds possessing a 4-(chloromethyl)-2(5H)-furanone structure and having the same HOMO characteristics. HOMO energies failed to correlate with mutagenicity. Neither computed atomic charge nor 13C chemical shift values for the larger compound group of 10 correlated well with mutagenicity or with each other. Sodium borohydride and borodeuteride reductions of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone demonstrated experimentally that hydride became attached to C-4.