On the origin of cytotoxicity of the natural product varacin. A novel example of a pentathiepin reaction that provides evidence for a triatomic sulfur intermediate

A density functional theoretical study is presented, which implicates a nov el S-3-cleavage in the decomposition of a pentathiepin. This study predicts an interconversion between a pentathiepin and an open-chain polysulfur ion intermediate from which a key determinant in the chemistry then follows. E xpulsion of diatomic sulfur, S-2, is unlikely from the unimolecular collaps e of the open-chain polysulfur ion. Instead, S-3 can dissociate due to an u nusually long and weak sulfur-sulfur (S4-S5) bond. A mechanistic picture no w emerges which predicts that the novel S-S cleavage reaction and the unant icipated S3 fragmentation are a result of delocalization. of the negative c harge within the remaining carbon-sulfur fragment. The computed results pre sented here reveal a new aspect to the chemistry of pentathiepins, that of S-3 unit transfer, which is proposed to have significance in the mechanism of cytotoxicity of the natural product varacin, 1.