Mutagenicity of chlorine‐substituted furanones and their inactivation by reaction with nucleophiles

摘要

AbstractThe reported high mutagenic potency of 3‐chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5H)‐furanone againstSalmonella typhimurium(TA100) was confirmed in the determined value of 6,300 net revertants/nmol. Partial inactivation of the furanone by Arochlor 1254‐induced rat liver homogenate fraction (S9) was observed. Inactivation by the nucleophiles hydroxide ion, SO2, S2O2/3−, pyrrolidine and glutathione, all in aqueous solutions, was determined and the results compared. Mutagenic reduction was observed for all of the nucleophiles but was most pronounced for glutathione. Inactivation by hydroxide ion was most sensitive in the pH range of 9 to 11, was associated with chloride ion formation and paralleled irreversible ultraviolet spectral change resulting in the loss of the 227 nm absorption maximum and the appearance of a new maximum at 255 nm. Neutral aqueous solutions of the furanone and glutathione were marked by two UV maxima, at 250 and 270 nm, and lacked the aldehydic1H‐NMR signal, which was observed in the spectrum of the neutral solution of the furanone alone and was attributed to the presence of its acyclic tautomeric form. Several other furanones were prepared. Their Ames mutagenicities and those of chlorine‐substituted intermediates obtained in the synthesis of the furanone were determined and compared, and then related to the reported mutagenicities of s