Unusual η 2 ‐Allene Osmacycle with Apoptotic Properties

Screening of a library of structurally unusual osmacyclic complexes for their antiproliferate properties in HeLa cells led to the discovery of a highly cytotoxic η 2 ‐allene osmacycle. In this remarkably stable complex, osmium constitutes part of a metallacycle through the formation of a σ‐bond to a carbon in combination with coordination to an allene moiety. The osmacycle strongly induces apoptosis in Burkitt‐like lymphoma cells at submicromolar concentrations. The reduction of the mitochondrial membrane potential, the induction of DNA fragmentation, and the activation of caspases‐9 and ‐3 reveal that programmed cell death occurs through the intrinsic mitochondrial pathway. From the lipophilic and cationic nature of the osmacycle, in addition to a low oxidation potential ( E 1/2 =+0.27 V vs. Fc/Fc + , Fc=ferrocene) it is proposed that mitochondria are the cellular target where oxidative decomposition initiates apoptosis.