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 novel 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. Expulsion of diatomic sulfur, S(2), is unlikely from the unimolecular collapse of the open-chain polysulfur ion. Instead, S(3) can dissociate due to an unusually long and weak sulfur-sulfur (S4-S5) bond. A mechanistic picture now emerges which predicts that the novel S-S cleavage reaction and the unanticipated S(3) fragmentation are a result of delocalization of the negative charge within the remaining carbon-sulfur fragment. The computed results presented 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.
Greer
A
A
Department of Chemistry, Graduate School and University Center and The City University of New York (CUNY), Brooklyn College, Brooklyn, New York 11210, USA.
D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity; D005021:Ethylamines / Q000737:chemistry* / Q000633:toxicity*; D008956:Models, Chemical; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000737:chemistry* / Q000633:toxicity*
D000970:Antineoplastic Agents; D005021:Ethylamines; D013440:Sulfides